Article Author:
Basil Peechakara
Article Editor:
Mohit Gupta
3/7/2019 9:38:49 AM
PubMed Link:


Ampicillin is FDA approved for the treatment of infections caused by specific bacteria. These infections include:

  • Respiratory tract infection, caused by Streptococcus pneumoniae, penicillinase- and non-penicillinase-producing Staphylococcus aureus, group A beta-hemolytic Streptococci, and Hemophilus influenzae.
  • Bacterial meningitis,[1] caused by gram-negative bacteria (Listeria monocytogens, Neisseria meningitidis), Escherichia coli and Group B Streptococci. Adding aminoglycosides increases its effectiveness against gram-negative bacteria.
  • Septicemia and endocarditis,[2] caused by gram-positive bacteria including penicillin-susceptible Staphylococci, all Streptococcus species, and enterococci.
  • Gram negative bacteria including E. coli, all Salmonella species, and Proteus mirabilis.
  • Genitourinary infections, caused by sensitive strains of E. coli and P. mirabilis.
  • Gastrointestinal infections, caused by Salmonella Typhi, all Shigella species, and other Salmonella species. These usually improve with oral or intravenous therapy. A culture must be obtained for susceptibility and antibiotic sensitivity. However, empiric therapy may be started before the results are available.

Endocarditis caused by enterococci usually responds to intravenous ampicillin. Adding aminoglycosides with ampicillin may increase its effectiveness when treating endocarditis caused by streptococci.

Mechanism of Action

The mode of action of beta-lactam antibiotics on sensitive organisms can be considered a two-step process. In the first step, the drug binds to primary receptors called membrane-bound penicillin-binding proteins (PBPs). These proteins perform vital roles in cell cycle-related, morphogenetic formation of cell wall peptidoglycan. The inactivation of PBPs by bound antibiotic has immediate, arresting actions on their function. The second stage consists of the physiological effects caused by this receptor-ligand interaction. PBPs are involved in the late stages of peptidoglycan synthesis in the cell wall. Because peptidoglycan maintains the integrity of the cell wall which resides in a hypotonic environment, its disruption causes lysis and cell death.[3]


Ampicillin may be administered orally, intramuscularly, or intravenously. 

Parenteral administration is preferable for severe or moderately severe infections. The oral route should not be the initial therapy in life-threatening conditions, and it should always be followed after parenteral therapy.

When administered orally, ampicillin is given on an empty stomach with one or two full glasses of water to increase absorption.

For intravenous administration, ampicillin may be delivered as an intravenous bolus. Reconstitution of vials containing 125, 250, or 500 mg of the drug with 5 mL bacteriostatic or sterile water is recommended. Vials containing 1 or 2 g should be reconstituted with 7.4 or 14.8 mL, respectively, of bacteriostatic or sterile water.

If ampicillin is administered intramuscularly, it should be injected into a large muscle mass. Reconstitute with bacteriostatic or sterile water to create solutions containing 125 or 250 mg/mL.

Rate of administration

Formulations reconstituted from 125, 250, or 500 mg vials must be given over a period of 3 to 5 minutes by intravenous injection.

Formulations reconstituted from 1 or 2 g vials must be given over a period of over 10 to 15 minutes by intravenous injection.

The half-life of ampicillin is 0.7 to 1.5 hours in adults with normal kidney function. 

Adverse Effects

The primary adverse effects for ampicillin include seizure, diarrhea, enterocolitis, pseudomembranous colitis, vomiting, agranulocytosis, hemolytic anemia, eosinophilia, and immune thrombocytopenia. 

Common Adverse Effects


Stomatitis, glossitis, black 'hairy' tongue, nausea, vomiting, pseudomembranous colitis, enterocolitis, and diarrhea. These effects mainly arise from oral dose administration.

Hypersensitivity reactions

Skin rashes and urticaria are frequently reported. Some cases of erythema multiforme and exfoliative dermatitis have also been reported. Anaphylaxis is the most serious complication experienced and is usually associated with the parenteral form.


A moderate elevation of serum glutamic oxaloacetic transaminase is reported, commonly in infants. Its significance is unknown. Mild transient elevations are noted with repeated intramuscular administrations in individuals receiving larger-than-usual doses. Evidence indicates that serum glutamic oxaloacetic transaminase is released in the intramuscular injection site. The increased quantities seen in blood may not necessarily be from the liver as a source.

Hemato-lymphatic systems

Anemia, thrombocytopenic purpura, thrombocytopenia, eosinophilia, agranulocytosis, and leukopenia are reported during ampicillin therapy. These reactions are reversible on discontinuation of treatment, the etiology being a hypersensitive phenomenon.

Opportunistic infections

During therapy, there is a possibility of superinfection with some bacteria or mycotic organisms. In such cases, discontinuation of treatment and substitution of the appropriate therapy is appropriate.

Central nervous system



Ampicillin is contraindicated in the treatment of infections caused by penicillinase-producing organisms. 

Serious and life-threatening anaphylactoid reactions have been reported with penicillin therapy. Although anaphylaxis is more common following parenteral therapy, it has also been demonstrated after oral administration. It is more apt in a patient with previous history of penicillin hypersensitivity and/or reaction to multiple allergens. Before initiating therapy, a careful inquiry should be made relating to hypersensitivity reactions to cephalosporins, allergens, or penicillin. If a hypersensitivity reaction occurs, the therapy should be discontinued, and alternative therapy should be initiated. Anaphylactoid reactions require immediate emergency treatment with oxygen, epinephrine, steroids, and airway management, including intubation if indicated.

Antibacterial treatment also alters the natural flora of the intestine, leading to overgrowth of Clostridium difficile. C. difficile-associated diarrhea (CDAD) is reported with nearly all antibacterial agent use, especially ampicillin. The resulting severity may range from mild diarrhea to fulminant colitis. Hypertoxin-producing C. difficile strains cause increased morbidity and mortality, as these strains are refractory to the recommended antimicrobial therapy and may require colectomy. CDAD may be considered with all patients after antibacterial use who present with diarrhea. Since it is reported to occur over two months after the administration of antibacterial agents, a careful medical history is necessary in these cases.

If CDAD is confirmed, ongoing antibiotic use not directed against the organism might need to be discontinued. Adequate fluid and electrolyte management, protein supplementation, the antibiotic regimen of C. difficile, and surgical evaluation should be considered if indicated. 

Roughly 43% of patients with infectious mononucleosis who start on ampicillin develop a rash. Ideally, the rash appears 7 to 10 days following the initiation of ampicillin therapy and remains for a few days to one week after the drug is discontinued. In most cases, the rash is maculopapular, generalized, and pruritic. Therefore, ampicillin administration is not recommended in these patients. Whether these patients are truly allergic to penicillin remains unknown.

Ampicillin administration without a clear indication of a strongly suspected or proven bacterial infection, or a prophylactic indication, is not likely to result in a benefit to the patient. Instead, it increases the risk of growth of drug-resistant bacteria.


When administering a prolonged therapy, monitor renal, hepatic, and hematologic functions periodically. Additionally, watch for signs of anaphylaxis during the first dose.


In cases of overdose, discontinuation of the medication, symptomatic treatment, and supportive care institution are required. In patients with decreased renal function, the antibiotic can be removed via hemodialysis but not peritoneal dialysis.

Enhancing Healthcare Team Outcomes

Ampicillin is often prescribed by many healthcare workers including the nurse practitioner. However, we have entered an era of drug resistance and it is important for all healthcare workers to not empirically prescribe ampicillin for every type of infection.


[1] Biggs BA,Kucers A, Penicillins and related drugs. The Medical journal of Australia. 1986 Dec 1-15     [PubMed PMID: 3540540]
[2] Wilson WR,Karchmer AW,Dajani AS,Taubert KA,Bayer A,Kaye D,Bisno AL,Ferrieri P,Shulman ST,Durack DT, Antibiotic treatment of adults with infective endocarditis due to streptococci, enterococci, staphylococci, and HACEK microorganisms. American Heart Association. JAMA. 1995 Dec 6     [PubMed PMID: 7474277]
[3] Tipper DJ, Mode of action of beta-lactam antibiotics. Pharmacology     [PubMed PMID: 3889939]