Ampicillin

• Bacterial meningitis; an aminoglycoside can be added to increase efficacy against gram-negative meningitis bacteria[11]
• Endocarditis by enterococcal strains (off-label use); often given with an aminoglycoside[12]
• Gastrointestinal infections caused by contaminated water or food (for example, by Salmonella)[11]
• Genito-urinary tract infections[11]
• Healthcare-associated infections that are related to infections from using urinary catheters and that are unresponsive to other medications[13]
• Otitis media (middle ear infection)
• Prophylaxis (i.e. to prevent infection) in those who previously had rheumatic heart disease or are undergoing dental procedures, vaginal hysterectomies, or C-sections.[5] It is also used in pregnant woman who are carriers of group B streptococci to prevent early-onset neonatal infections.[5]
• Respiratory infections, including bronchitis, pharyngitis[11]
• Sinusitis
• Sepsis[14]
• Whooping cough, to prevent and treat secondary infections[5]

Ampicillin used to also be used to treat gonorrhea, but there are now too many strains resistant to penicillins.[5]

Ampicillin is used to treat infections by many gram-positive and gram-negative bacteria. It was the first "broad spectrum" penicillin with activity against gram-positive bacteria, including Streptococcus pneumoniae, Streptococcus pyogenes, some isolates of Staphylococcus aureus (but not penicillin-resistant or methicillin-resistant strains), Trueperella, and some Enterococcus. It is one of the few antibiotics that works against multidrug resistant Enterococcus faecalis and E. faecium.[15] Activity against gram-negative bacteria includes Neisseria meningitidis, some Haemophilus influenzae, and some of the Enterobacteriaceae (though most Enterobacteriaceae and Pseudomonas are resistant).[15][16] 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.[17][18] It is sometimes used in combination with other antibiotics that have different mechanisms of action, like vancomycin, linezolid, daptomycin, and tigecycline.[19][20]

Ampicillin can be administered by mouth, an intramuscular injection (shot) or by intravenous infusion.[5] The oral form, available as capsules or oral suspensions, is not given as an initial treatment for severe infections, but rather as a follow-up to an IM or IV injection.[5] For IV and IM injections, ampicillin is kept as a powder that must be reconstituted.[21]

IV injections must be given slowly, as rapid IV injections can lead to convulsive seizures.[5][22]

Ampicillin is one of the most used drugs in pregnancy,[23] and has been found to be generally harmless both by the Food and Drug Administration in the U.S. (which classified it as category B) and the Therapeutic Goods Administration in Australia (which classified it as category A).[5][24] It is the drug of choice for treating Listeria monocytogenes in pregnant women, either alone or combined with an aminoglycoside.[5] Pregnancy increases the clearance of ampicillin by up to 50%, and a higher dose is thus needed to reach therapeutic levels.[23][25]

Ampicillin crosses the placenta and remains in the amniotic fluid at 50–100% of the concentration in maternal plasma; this can lead to high concentrations of ampicillin in the newborn.[25]

While lactating mothers secrete some ampicillin into their breast milk, the amount is minimal.[5][23]

In newborns, ampicillin has a longer half-life and lower plasma protein binding.[26] The clearance by the kidneys is lower, as kidney function has not fully developed.[5]

Ampicillin overdose can cause behavioral changes, confusion, blackouts, and convulsions, as well as neuromuscular hypersensitivity, electrolyte imbalance, and kidney failure.[11]

The amino group (highlighted in magenta) is present on ampicillin but not penicillin G.

Ampicillin is in the penicillin group of beta-lactam antibiotics and is part of the aminopenicillin family. It is roughly equivalent to amoxicillin in terms of activity.[5] Ampicillin is able to penetrate gram-positive and some gram-negative bacteria. It differs from penicillin G, or benzylpenicillin, only by the presence of an amino group. 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 E. coli, Proteus mirabilis, Salmonella enterica, and Shigella.[17][34]

Ampicillin acts as an irreversible inhibitor of the enzyme transpeptidase, which is needed by bacteria to make the cell wall.[5] It inhibits the third and final stage of bacterial cell wall synthesis in binary fission, which ultimately leads to cell lysis; therefore, ampicillin is usually bacteriolytic.[5][35]

Ampicillin is well-absorbed from the GI tract (though food reduces its absorption), and reaches peak concentrations in one to two hours. The bioavailability is around 62% for parenteral routes. Unlike other penicillins, which usually bind 60–90% to plasma proteins, ampicillin binds to only 15–20%.[5][26]

Ampicillin is distributed through most tissues, though it is concentrated in the liver and kidneys. It can also be found in the cerebrospinal fluid when the meninges become inflamed (such as, for example, meningitis).[26] Some ampicillin is metabolized by hydrolyzing the beta-lactam ring to penicilloic acid,[5] though most of it is excreted unchanged.[11] 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.

Hetacillin and pivampicillin are ampicillin esters that have been developed to increase bioavailability.[36]