Ampicillin exerts its action on growing and dividing bacteria by inhibiting bacterial cell wall synthesis. Benzylpenicillin inhibits the final cross-linking stage of peptidoglycan production by binding to and inactivating transpeptidases (penicillin-binding protein on the surface of the bacterial cell membrane) causing the cell wall to rupture by osmotic pressure. It is now realised that other earlier stages in cell-wall synthesis can also be inhibited by Ampicillin.
Ampicillin is bactericidal for both Gram-positive and Gram-negative organisms.
Gram-Positive Organisms: Ampicillin is active against Strep. Pyogenes, Strep. Pneumoniae
and Strep. Viridans
. Pneumococcal strains which are relatively resistant to penicillin G are more sensitive to Ampicillin. Group B Streptococci are always Ampicillin sensitivite, in addition Ampicillin combines with aminoglycosides such as Kanamycin, gentamicin, tobramycin or amikacin acts synergistically against these organisms resulting in accelerated streptococcal killing.
is usually sensitive to Ampicillin and often more so than penicillin G. The combination of ampicillin with streptomycin or kanamycin is synergistic against 50-75% of Strep. faecalis
, whereas Ampicillin plus gentamicin or tobramycin is synergistic against nearly all such strains. Anaerobic Gram-positive cocci such as peptococcus and peptostreptococcus spp. and anaerobic streptococci are nearly always Ampicillin sensitive.
Ampicillin is destroyed by staphylococcal beta lactamase, so that most Staph. aureus
and hospital acquired Staph. epidermidis
are Ampicillin resistant. Staph. saprophyticus
and other coagulase negative staphylococci such as Staph. hominis
which may be urethral isolates of young females are Ampicillin sensitive. C. diptheriae
and B. anthracis
are sensitive to Ampicillin. L. monocytogens
is also usually sensitive to Ampicillin. Most Nocardia
spp. strains are Ampicillin resistant. Anaerobic Gram-positive sporing bacillin such as Cl. Tetani, CI. Perfringens
(welchii), Cl. Botulinum
and other Clostridium
spp. are usually Ampicillin sensitive.
Ampicillin is nearly always active against anaerobic Gram-positive asporogenous bacilli such as Actinomyces, Eubacterium, Arachnia, Propionibacterium, Bifidobacterium and Lactobacillus.
Gram-negative Organism: Ampicillin is active against many enterobacteriaceae. E. coli
may be sensitive but many strains are resistant. Ampicillin resistance of E. coli
is nearly always due to beta lactamase production. Proteus mirabilis
is usually sensitive unless it is a beta lactamase producing strain.
spp. is usually susceptible to Ampicillin. The Brucella
spp. and B. pertussis
are consistently sensitive to Ampicillin. The same is true of N. meningitidis
. Branhamella catarrhalis
is Ampicillin sensitive expect strains producing beta lactamase. V. cholerae
and Campylobacter jejuni
are usually sensitive. Gardnerella vaginalis
is Ampicillin sensitive.
Some Gram-negative anaerobic bacteria such as B. melaninogenicus
spp. are usually Ampicillin sensitive. Other bacteroides
spp. vary in sensitivity but about 50% of isolates are inhibited by low concentrations.
Pharmacokinetics: Absorption and Serum level:
Ampicillin is given by injection as the sodium salt. After intramuscular administration of 500 mg, a serum peak of 7-14 mg/lit can be expected after 1 hour.
The half life of Ampicillin is 1-2 hours and the plasma protein binding is around 20%.
Ampicillin is distributed throughout the body and is to be found at lower concentration than in serum at most sites with the exception of the liver and kidneys. Penetration of the blood-barrier is poor except during active inflammation when a daily dose of 150 mg Ampicilin per kg may result in CSF level around 3 mg/lit.
Adequate therapeutic levels are reached in pleural, synovial and ocular fluids. Ampicillin crosses amniotic fluids during the first trimester do not reach therapeutic concentration. Some Ampicillin is secreted in the milk of a nursing mother.
Hepatic metabolism is a relatively unimportant route of Ampicillin elimination. About 10% of the dose in metabolised in the liver to the inactive penicilloic acid. Ampicillin esters are metabolised in the gut to the active from of the drug.
Renal clearance of Ampicillin is slower than that of benzylpenicillin, accounting for the longer half life. Renal excretion is both by glomerular filtration & by tubular secretion. At normal oral doses 30% Ampicillin is excreted in the urine resulting in levels between 250 mg/lit & 75% of the dose may be recovered unchanged from the urine in the same period. This can be reduced by simultaneous dosage with probenecid. The half life of Ampicillin may be prolonged in patients with renal failure through no adjustment of dose is likely to be necessary, other than in very severe cases. Ampicillin is also excreted in the bile, but levels are variable & have a particular tendency to be low in the presence of a non-functional gallbladder. There is a small enterohepatic circulation of the drug & the unexcreated agent is inactivated in the liver at a slower rate than Benzylpenicillin. The kinetic of Ampicillin are unlikely to be altered in patients with hepatic dysfunction. (See table.)
Click on icon to see table/diagram/image
Long term studies have not revealed any serious toxicity associated with Ampicillin.
Toxicology and carcinogenesis studies of Ampicillin was performed in F344/N rats and B6C3FI mice. In these studies Ampicillin was administered for 2 years to rats at doses of 0, 750 or 1500 mg and to mice at doses 0, 1500 or 3000 mg/kg. The drug was administered by oral gavage in corn oil. No toxic manifestations other than toxic lesions of the stomach were seen in rats and mice after Ampicillin administration.