Ampicillin
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Ampicillin is an
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...
belonging to the aminopenicillin class of the
penicillin Penicillins (P, PCN or PEN) are a group of beta-lactam antibiotic, β-lactam antibiotics originally obtained from ''Penicillium'' Mold (fungus), moulds, principally ''Penicillium chrysogenum, P. chrysogenum'' and ''Penicillium rubens, P. ru ...
family. The drug is used to prevent and treat several bacterial infections, such as respiratory tract infections, urinary tract infections,
meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, intense headache, vomiting and neck stiffness and occasion ...
,
salmonellosis Salmonellosis is a symptomatic infection caused by bacteria of the ''Salmonella'' type. It is the most common disease to be known as food poisoning (though the name refers to food-borne illness in general). These are defined as diseases, usuall ...
, and endocarditis. It may also be used to prevent group B streptococcal infection in newborns. It is used by mouth, by injection into a muscle, or intravenously. Common side effects include rash, nausea, and diarrhea. It should not be used in people who are allergic to penicillin. Serious side effects may include ''Clostridioides difficile'' colitis or anaphylaxis. While usable in those with kidney problems, the dose may need to be decreased. Its use during
pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...
and
breastfeeding Breastfeeding, also known as nursing, is the process where breast milk is fed to a child. Infants may suck the milk directly from the breast, or milk may be extracted with a Breast pump, pump and then fed to the infant. The World Health Orga ...
appears to be generally safe. Ampicillin was discovered in 1958 and came into commercial use in 1961. It is on the World Health Organization's List of Essential Medicines. The World Health Organization classifies ampicillin as critically important for human medicine. It is available as a generic medication.


Medical uses


Diseases

* Bacterial meningitis; an aminoglycoside can be added to increase efficacy against gram-negative meningitis bacteria * Endocarditis by enterococcal strains (off-label use); often given with an aminoglycoside * Gastrointestinal infections caused by contaminated water or food (for example, by ''
Salmonella ''Salmonella'' is a genus of bacillus (shape), rod-shaped, (bacillus) Gram-negative bacteria of the family Enterobacteriaceae. The two known species of ''Salmonella'' are ''Salmonella enterica'' and ''Salmonella bongori''. ''S. enterica'' ...
'') * Genito-urinary tract infections * Healthcare-associated infections that are related to infections from using urinary catheters and that are unresponsive to other medications * 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. It is also used in pregnant woman who are carriers of group B streptococci to prevent early-onset neonatal infections. * Respiratory infections, including bronchitis, pharyngitis * Sinusitis *
Sepsis Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage of sepsis is followed by suppression of the immune system. Common signs and s ...
* Whooping cough, to prevent and treat
secondary infection infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
s Ampicillin used to also be used to treat gonorrhea, but there are now too many strains resistant to penicillins.


Bacteria

Ampicillin is used to treat infections by many
gram-positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. The Gram stain is ...
and
gram-negative bacteria Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the Crystal violet, crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelo ...
. It was the first "broad spectrum" penicillin with activity against gram-positive bacteria, including '' Streptococcus pneumoniae'', '' Streptococcus pyogenes'', some isolates of ''
Staphylococcus aureus ''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often posi ...
'' (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''. Activity against gram-negative bacteria includes '' Neisseria meningitidis'', some '' Haemophilus influenzae'', and some of the Enterobacteriaceae (though most Enterobacteriaceae and '' Pseudomonas'' are resistant). 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. It is sometimes used in combination with other antibiotics that have different mechanisms of action, like
vancomycin Vancomycin is a glycopeptide antibiotic medication used to treat certain bacterial infections. It is administered intravenously ( injection into a vein) to treat complicated skin infections, bloodstream infections, endocarditis, bone an ...
, linezolid, daptomycin, and tigecycline.


Available forms

Ampicillin can be administered by
mouth A mouth also referred to as the oral is the body orifice through which many animals ingest food and animal communication#Auditory, vocalize. The body cavity immediately behind the mouth opening, known as the oral cavity (or in Latin), is also t ...
, an
intramuscular injection Intramuscular injection, often abbreviated IM, is the medical injection, injection of a substance into a muscle. In medicine, it is one of several methods for parenteral, parenteral administration of medications. Intramuscular injection may be ...
(shot) or by intravenous infusion. 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. For IV and IM injections, ampicillin is kept as a powder that must be reconstituted. IV injections must be given slowly, as rapid IV injections can lead to convulsive
seizures A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...
.


Specific populations

Ampicillin is one of the most used drugs in pregnancy, and has been found to be generally harmless both by the
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...
in the U.S. (which classified it as category B) and the Therapeutic Goods Administration in Australia (which classified it as category A). It is the drug of choice for treating '' Listeria monocytogenes'' in pregnant women, either alone or combined with an aminoglycoside. Pregnancy increases the clearance of ampicillin by up to 50%, and a higher dose is thus needed to reach therapeutic levels. 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. While lactating mothers secrete some ampicillin into their breast milk, the amount is minimal. In newborns, ampicillin has a longer half-life and lower plasma protein binding. The clearance by the kidneys is lower, as kidney function has not fully developed.


Contraindications

Ampicillin is contraindicated in those with a hypersensitivity to penicillins, as they can cause fatal anaphylactic reactions. Hypersensitivity reactions can include frequent skin rashes and hives, exfoliative dermatitis, erythema multiforme, and a temporary decrease in both red and white blood cells. Ampicillin is not recommended in people with concurrent mononucleosis, as over 40% of patients develop a skin rash.


Side effects

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 Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include Allergic rhinitis, hay fever, Food allergy, food al ...
. 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). Some develop black "furry" tongue. Serious adverse effects also include seizures and
serum sickness Serum sickness in humans is a adverse drug reaction, reaction to proteins in antiserum derived from a non-human animal source, occurring 5–10 days after exposure. Symptoms often include a rash, Arthralgia, joint pain, fever, and lymphadenopathy. ...
. The most common side effects, experienced by about 10% of users are diarrhea and rash. Less common side effects can be nausea, vomiting, itching, and blood dyscrasias. The gastrointestinal effects, such as hairy tongue, nausea, vomiting, diarrhea, and colitis, are more common with the oral form of penicillin. Other conditions may develop up several weeks after treatment.


Overdose

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


Interactions

Ampicillin reacts with probenecid and methotrexate to decrease renal excretion. 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 has been said to make oral contraceptives less effective, but this has been disputed. It can be made less effective by other antibiotic, such as chloramphenicol, erythromycin,
cephalosporins The cephalosporins (sg. ) are a class of β-lactam antibiotics originally derived from the fungus ''Acremonium'', which was previously known as ''Cephalosporium''. Together with cephamycins, they constitute a subgroup of β-lactam antibiotic ...
, and tetracyclines. For example, tetracyclines inhibit protein synthesis in bacteria, reducing the target against which ampicillin acts. If given at the same time as aminoglycosides, it can bind to it and inactivate it. When administered separately, aminoglycosides and ampicillin can potentiate each other instead. Ampicillin causes skin rashes more often when given with allopurinol. Both the live cholera vaccine and live typhoid vaccine can be made ineffective if given with ampicillin. Ampicillin is normally used to treat cholera and typhoid fever, lowering the immunological response that the body has to mount.


Pharmacology


Mechanism of action

Ampicillin is in the
penicillin Penicillins (P, PCN or PEN) are a group of beta-lactam antibiotic, β-lactam antibiotics originally obtained from ''Penicillium'' Mold (fungus), moulds, principally ''Penicillium chrysogenum, P. chrysogenum'' and ''Penicillium rubens, P. ru ...
group of beta-lactam antibiotics and is part of the aminopenicillin family. It is roughly equivalent to amoxicillin in terms of activity. 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 ''
Escherichia coli ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Escherichia'' that is commonly fo ...
'', '' Proteus mirabilis'', '' Salmonella enterica'', and '' Shigella''. Ampicillin acts as an irreversible inhibitor of the enzyme transpeptidase, which is needed by bacteria to make the cell wall. 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.


Pharmacokinetics

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%. 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). Some ampicillin is metabolized by hydrolyzing the beta-lactam ring to penicilloic acid, though most of it is excreted unchanged. In the kidneys, it is filtered out mostly by tubular secretion; some also undergoes glomerular filtration, and the rest is excreted in the
feces Feces (also known as faeces American and British English spelling differences#ae and oe, or fæces; : faex) are the solid or semi-solid remains of food that was not digested in the small intestine, and has been broken down by bacteria in the ...
and bile. Hetacillin and pivampicillin are ampicillin
esters In chemistry, an ester is a chemical compound, compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds c ...
that have been developed to increase bioavailability.


History

Ampicillin has been used extensively to treat bacterial infections since 1961. 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. Ampicillin (originally branded as "Penbritin") also demonstrated activity against gram-negative organisms such as ''H. influenzae'', coliforms, and '' Proteus'' spp.


Society and culture


Economics

Ampicillin is relatively inexpensive. In the United States, it is available as a generic medication.


Veterinary use

In veterinary medicine, ampicillin is used in cats, dogs, and farm animals to treat: * Anal gland infections * Cutaneous infections, such as abscesses, cellulitis, and pustular dermatitis * '' E. coli'' and ''Salmonella'' infections in cattle, sheep, and goats (oral form). Ampicillin use for this purpose had declined as bacterial resistance has increased. * Mastitis in sows * Mixed aerobic–anaerobic infections, such as from cat bites * Multidrug-resistant ''Enterococcus faecalis'' and ''E. faecium'' * Prophylactic use in poultry against ''Salmonella'' and sepsis from ''E. coli'' or ''Staphylococcus aureus'' * Respiratory tract infections, including tonsilitis, bovine respiratory disease, shipping fever, bronchopneumonia, and calf and bovine pneumonia * Urinary tract infections in dogs Horses are generally not treated with oral ampicillin, as they have low bioavailability of beta-lactams. The half-life in animals is around that same of that in humans (just over an hour). Oral absorption is less than 50% in cats and dogs, and less than 4% in horses.


References


External links

* * * {{Authority control Enantiopure drugs Penicillins Phenyl compounds World Health Organization essential medicines Wikipedia medicine articles ready to translate