AMPICILLIN SODIUM

General Administration Information
For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Oral Administration
-All dosage forms: Take on an empty stomach (i.e., at least 30 minutes prior to or 2 hours after a meal).
Oral Liquid Formulations
-Shake well prior to each use.
Reconstitution
-Review the manufacturer reconstitution instructions for the particular product and package size.
-Add water in 2 portions and shake well after each addition.
-Storage: Store reconstituted suspension in refrigerator; discard after 14 days.



Injectable Administration
-Ampicillin sodium may be administered intramuscularly (IM), by slow intravenous (IV) push, or by IV infusion.
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
-Do not administer ampicillin at the same time or mix in the same container as aminoglycosides. Beta-lactam antibiotics such as ampicillin may inactivate aminoglycoside antibiotics when combined.
Intravenous Administration
IV Push

Reconstitution
-Bacteriostatic Water for Injection should not be used for preparation of neonatal doses.
-125 mg, 250 mg, and 500 mg vials: Reconstitute the 125 mg, 250 mg, and 500 mg vials with 5 mL of Sterile Water for Injection or Bacteriostatic Water for Injection for a resultant concentration of 25 mg/mL, 50 mg/mL, and 100 mg/mL, respectively.
-1 and 2 g vials: Reconstitute the 1 g and 2 g vials with 7.4 or 14.8 mL of Sterile Water for Injection or Bacteriostatic Water for Injection, respectively, for a resultant concentration of 125 mg/mL.
-Swirl vial and ensure that all drug is completely dissolved into solution.
-Withdraw the appropriate dose from the vial and administer within 1 hour of reconstitution.
IV Push Administration

-125 mg, 250 mg, and 500 mg doses: Administer as slow IV push over at least 3 to 5 minutes.
-1 and 2 g doses: Administer as slow IV push over at least 10 to 15 minutes.
-Do not administer faster than recommended as more rapid administration may result in seizures.

Intermittent IV Infusion
Reconstitution/Dilution
-125 mg, 250 mg, and 500 mg vials: Reconstitute the 125 mg, 250 mg, and 500 mg vials with 5 mL of Sterile Water for Injection or Bacteriostatic Water for Injection for a resultant concentration of 25 mg/mL, 50 mg/mL, and 100 mg/mL, respectively.
-1 and 2 g vials: Reconstitute the 1 g and 2 g vials with 7.4 or 14.8 mL of Sterile Water for Injection or Bacteriostatic Water for Injection, respectively, for a resultant concentration of 125 mg/mL.
-Pharmacy Bulk Vial: The 10 g vial is designed for use in preparing multiple IV admixtures. Add 94 mL Sterile Water for Injection. The resulting solution will contain 100 mg/mL ampicillin and is stable up to 1 hour at room temperature.
-Once vials are prepared, withdraw the appropriate dose and further dilute with a compatible fluid (e.g., 0.9% NaCl Injection) to a usual concentration of 10 to 30 mg/mL.
-Stability is dependent on the diluent chosen, the final concentration, and the storage conditions and may range from 1 hour to 72 hours. Consult ampicillin full prescribing information (i.e., package insert) for detailed stability information.

Intermittent IV Infusion Administration
-Infuse appropriate dose IV over 15 to 30 minutes.

Intramuscular Administration
Reconstitution
-Reconstitute the 125 mg vial with 1.2 mL of Sterile Water for Injection or Bacteriostatic Water for Injection for a resultant concentration of 125 mg/mL. Reconstitute 250 mg, 500 mg, 1 g, and 2 g vials with 1 mL, 1.8 mL, 3.5 mL, and 6.8 mL of Sterile Water for Injection or Bacteriostatic Water for Injection, respectively, for a resultant concentration of 250 mg/mL.
-Administer within 1 hour of preparation.

Intramuscular (IM) Injection
-Withdraw appropriate dose and inject deeply into a large muscle mass (e.g., anterolateral thigh or deltoid [children and adolescents only]).
-In general, IM administration of antibiotics in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.

Although hypersensitivity reactions are among the most frequently reported adverse reactions to the penicillins, they are not common in neonates. Penicillin allergy has been reported in up to 20% of patients in the general population; however, around 90% of reported allergies are incorrectly reported and patients lack penicillin-specific IgE antibodies. The actual prevalence of penicillin allergy in the general population is likely no greater than 5%. Hypersensitivity reactions may include rash (unspecified), serum sickness, anaphylactoid reactions including anaphylactic shock, erythema multiforme, exfoliative dermatitis, maculopapular rash, pruritus, and urticaria. Rash may develop after the first week and may cover the entire body, including the soles, palms, and oral mucosa. The rash usually disappears in 3-7 days. Angioedema has also been reported with penicillins. The incidence of rash secondary to ampicillin seems to be higher in patients with viral illnesses, such as mononucleosis.

Hematologic effects seen with aminopenicillins, such as ampicillin, include anemia, thrombocytopenia, thrombotic thrombocytopenic purpura (TTP), eosinophilia, leukopenia, and agranulocytosis and are potentially associated with hypersensitivity reactions. These adverse hematologic effects are generally reversible after discontinuation of the aminopenicillin. Platelet dysfunction, prolonged bleeding time, and prolongation of APTT have been reported in patients receiving ampicillin. Prolongation of the bleeding time has been observed in neonates receiving ampicillin (50-100 mg/kg IV every 12 hours). In one study (n = 20) in very low birth-weight neonates, the bleeding time was prolonged by an average of 2 minutes after a longer course of ampicillin (10-15 doses). In another study (n = 15) in neonates, bleeding time was increased by approximately 60 seconds after the third and fourth doses of ampicillin. Positive direct Coombs' tests have been reported in patients receiving penicillins. If hematological testing is done, a positive Coombs' test should be considered as being possibly due to the antibiotic.

Ampicillin has been associated with acute generalized exanthematous pustulosis (AGEP). The non follicular, pustular, erythematous rash starts suddenly and is associated with fever above 38 degrees C. Drugs are the main cause of AGEP. A period of 2-3 weeks after an inciting drug exposure appears necessary for a first episode of AGEP. Unintentional reexposure may cause a second episode within 2 days.

In the general population, gastrointestinal adverse events may occur in 2-5% of patients receiving penicillins. Glossitis, black "hairy" tongue (tongue discoloration), diarrhea, nausea, vomiting, enterocolitis, sore mouth or tongue, and stomatitis are commonly reported gastrointestinal side effects during ampicillin therapy. Gastrointestinal adverse effects are associated more often with the oral formulation and are more common with oral ampicillin compared to oral amoxicillin.

Seizures have been reported with ampicillin and may occur when the intravenous product is administered faster than recommended.

Elevated hepatic enzymes, specifically a moderate rise in serum glutamic oxaloacetic transaminase (SGOT), has been reported, particularly in infants; however, the significance is unknown. Additionally, mild transient SGOT elevations have been observed in patients receiving 2-4 times the usual dose and in patients receiving repeated IM injections. Glutamic oxaloacetic transaminase (GOT) may be released at the site of IM injection and its presence may not be related to hepatic involvement.

Microbial overgrowth and superinfection can occur with antibiotic use. C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis has been reported with ampicillin. If pseudomembranous colitis is suspected or confirmed, ongoing antibacterial therapy not directed against C. difficile may need to be discontinued. Institute appropriate fluid and electrolyte management, protein supplementation, C. difficile-directed antibacterial therapy, and surgical evaluation as clinically appropriate.

Laryngeal stridor and high fever have been reported with ampicillin use; the incidence and relationship to the drug are unclear.

The Jarisch-Herxheimer reaction is a self-limiting systemic reaction that has been reported in the setting of spirochete infections, such as Lyme disease, syphilis, relapsing fever, and leptospirosis, after the initiation of antimicrobial therapy. It is characterized by fever, chills, myalgias, headache, exacerbation of cutaneous lesions, tachycardia, hyperventilation, vasodilation with flushing, and mild hypotension. Less commonly, symptoms may include meningitis, pulmonary failure, hepatic and renal dysfunction, myocardial injury, premature uterine contractions in pregnant patients, and worsening cerebral function as well as strokes and seizures. The reaction has been noted in up to 30% of patients with early Lyme disease. The timing of the reaction varies by underlying infection but typically presents within a few hours after the initiation of antibiotics. For Lyme disease, the reaction usually begins within 1 to 2 hours after starting therapy and disappears within 12 to 24 hours. The reaction after treatment in syphilis usually starts at 4 hours, peaks at 8 hours, and subsides by 16 hours whereas it starts at about 1 to 2 hours, peaks at 4 hours, and subsides by 8 hours after treatment in relapsing fever. The pathogenesis of this reaction is unknown but may be due to the release of spirochetal heat-stable pyrogen. Fluids and antipyretics can be used to alleviate symptoms and duration of the reaction if severe.

A false-positive reaction for glucose in the urine has been observed in patients receiving penicillins and using Benedict's solution, Fehling's solution, or Clinitest tablets for urine glucose testing. However, this reaction has not been observed with Tes-tape (glucose Enzymatic Test Strip, USP, Lilly) or Clinistix. Patients with diabetes who test their urine for glucose should use glucose tests based on enzymatic glucose oxidase reactions while on ampicillin treatment.

Ampicillin is a penicillin and should not be used in patients with a penicillin hypersensitivity. Ampicillin should also be used cautiously in patients with cephalosporin hypersensitivity and carbapenem hypersensitivity. These patients are more susceptible to hypersensitivity reactions during therapy with ampicillin. Patients with allergies or allergic conditions including asthma, eczema, hives (urticaria), or hay fever may have a greater risk for hypersensitivity reactions to penicillins.

Ampicillin should be used with caution in patients with renal disease or renal impairment since the drug is eliminated by the kidneys. Ampicillin dosage interval should be adjusted in those patients with CrCl <= 50 ml/min and in those patients with renal failure. Supplemental doses are recommended for patients receiving dialysis. During prolonged therapy in patients without preexisting renal impairment, renal function should be periodically evaluated.

Ampicillin should be used with caution in patients with mononucleosis as a high incidence (43-100%) of skin rashes has been reported in these patients. The rash (maculopapular, pruritic, and generalized) typically appears 7-10 days after therapy initiation and resolves a few days to a week after treatment is discontinued.

Oral ampicillin is contraindicated for the treatment of infections caused by penicillinase-producing organisms due to antimicrobial resistance. In general, any ampicillin product will not treat organisms that are penicillinase-producing. Antibiotic therapy can result in superinfection or suprainfection with non susceptible organisms. Overgrowth of Candida can occur during antibiotic therapy. Patients should be monitored closely during therapy.

Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including ampicillin, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

Description: Ampicillin is classified as an aminopenicillin. The aminopenicillins, a group of antibiotics that includes amoxicillin, are able to penetrate gram-negative bacteria more readily than are the natural penicillins or penicillinase-resistant penicillins. However, the aminopenicillins are not stable to beta-lactamases of either gram-positive or gram-negative bacteria. In combination with sulbactam (a beta-lactamase inhibitor), ampicillin's spectrum is broadened to include many of these beta-lactamase-producing organisms. Compared with amoxicillin, oral ampicillin has a lower bioavailability and is more likely to cause adverse GI reactions. Ampicillin is commonly used in combination with gentamicin in neonates for suspected infection and for endocarditis and community-acquired pneumonia caused by susceptible organisms in other populations. Ampicillin is FDA-approved for use in pediatric patients, although the exact age range is not specified.

Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Bacillus anthracis, Clostridium sp., Enterococcus sp., Escherichia coli, Haemophilus influenzae (beta-lactamase negative), Listeria monocytogenes, Neisseria gonorrhoeae, Neisseria meningitidis, Proteus mirabilis, Salmonella enterica serotype Typhi , Salmonella sp., Shigella sp., Staphylococcus sp., Streptococcus agalactiae (group B streptococci), Streptococcus dysgalactiae, Streptococcus pneumoniae, Streptococcus pyogenes (group A beta-hemolytic streptococci), Streptococcus sp., Viridans streptococci
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.

This drug may also have activity against the following microorganisms: Leptospira sp.
NOTE: Some organisms may not have been adequately studied during clinical trials; therefore, exclusion from this list does not necessarily negate the drug's activity against the organism.

For the treatment of meningitis and ventriculitis*:
-for the treatment of Listeria meningitis:
Intravenous or Intramuscular dosage:
Neonates 0 to 7 days: 100 mg/kg/dose IV every 8 hours for at least 21 days; consider the addition of an aminoglycoside. The FDA-approved dosage is 50 mg/kg/dose IV every 12 hours for neonates 34 weeks gestation and younger and 50 mg/kg/dose IV every 8 hours for neonates older than 34 weeks gestation.
Neonates older than 7 days: 75 mg/kg/dose IV every 6 hours for at least 21 days; consider the addition of an aminoglycoside. The FDA-approved dosage is 75 mg/kg/dose IV every 12 hours for neonates 34 weeks gestation and younger and 50 mg/kg/dose IV every 8 hours for neonates older than 34 weeks gestation.
Infants, Children, and Adolescents: 300 to 400 mg/kg/day (Max: 12 g/day) IV divided every 4 to 6 hours for at least 21 days; consider the addition of an aminoglycoside. The FDA-approved dosage is 150 to 200 mg/kg/day IV or IM divided every 3 to 4 hours.
-for the treatment of meningococcal meningitis as well as meningitis due to H. influenzae:
Intravenous or Intramuscular dosage:
Neonates 0 to 7 days: 100 mg/kg/dose IV every 8 hours for 7 days. The FDA-approved dosage is 50 mg/kg/dose IV every 12 hours for neonates 34 weeks gestation and younger and 50 mg/kg/dose IV every 8 hours for neonates older than 34 weeks gestation.
Neonates older than 7 days: 75 mg/kg/dose IV every 6 hours for 7 days. The FDA-approved dosage is 75 mg/kg/dose IV every 12 hours for neonates 34 weeks gestation and younger and 50 mg/kg/dose IV every 8 hours for neonates older than 34 weeks gestation.
Infants, Children, and Adolescents: 300 to 400 mg/kg/day (Max: 12 g/day) IV divided every 4 to 6 hours for 7 days. The FDA-approved dosage is 150 to 200 mg/kg/day IV or IM divided every 3 to 4 hours.
-for the treatment of meningitis due to S. agalactiae (group B streptococcal meningitis):
Intravenous or Intramuscular dosage:
Neonates 0 to 7 days: 100 mg/kg/dose IV every 8 hours for 14 to 21 days; consider the addition of an aminoglycoside. The FDA-approved dosage is 50 mg/kg/dose IV every 12 hours for neonates 34 weeks gestation and younger and 50 mg/kg/dose IV every 8 hours for neonates older than 34 weeks gestation.
Neonates older than 7 days: 75 mg/kg/dose IV every 6 hours for 14 to 21 days; consider the addition of an aminoglycoside. The FDA-approved dosage is 75 mg/kg/dose IV every 12 hours for neonates 34 weeks gestation and younger and 50 mg/kg/dose IV every 8 hours for neonates older than 34 weeks gestation.
Infants, Children, and Adolescents: 300 to 400 mg/kg/day (Max: 12 g/day) IV divided every 4 to 6 hours for 14 to 21 days; consider the addition of an aminoglycoside. The FDA-approved dosage is 150 to 200 mg/kg/day IV or IM divided every 3 to 4 hours.
-for the treatment of pneumococcal meningitis*:
Intravenous dosage:
Neonates 0 to 7 days: 100 mg/kg/dose IV every 8 hours for 10 to 14 days.
Neonates older than 7 days: 75 mg/kg/dose IV every 6 hours for 10 to 14 days.
Infants, Children, and Adolescents: 300 to 400 mg/kg/day (Max: 12 g/day) IV divided every 4 to 6 hours for 10 to 14 days.
-for the treatment of enterococcal meningitis*:
Intravenous dosage:
Neonates 0 to 7 days: 100 mg/kg/dose IV every 8 hours in combination with gentamicin for 14 to 21 days.
Neonates older than 7 days: 75 mg/kg/dose IV every 6 hours in combination with gentamicin for 14 to 21 days.
Infants, Children, and Adolescents: 300 to 400 mg/kg/day (Max: 12 g/day) IV divided every 4 to 6 hours in combination with gentamicin for 14 to 21 days.
-for the treatment of meningitis due to aerobic gram-negative rods:
Intravenous or Intramuscular dosage:
Neonates 0 to 7 days: 100 mg/kg/dose IV every 8 hours for 2 weeks beyond the first sterile CSF culture or at least 21 days, whichever is longer. The FDA-approved dosage is 50 mg/kg/dose IV every 12 hours for neonates 34 weeks gestation and younger and 50 mg/kg/dose IV every 8 hours for neonates older than 34 weeks gestation.
Neonates older than 7 days: 75 mg/kg/dose IV every 6 hours for 2 weeks beyond the first sterile CSF culture or at least 21 days, whichever is longer. The FDA-approved dosage is 75 mg/kg/dose IV every 12 hours for neonates 34 weeks gestation and younger and 50 mg/kg/dose IV every 8 hours for neonates older than 34 weeks gestation.
Infants, Children, and Adolescents: 300 to 400 mg/kg/day (Max: 12 g/day) IV divided every 4 to 6 hours for 21 days. The FDA-approved dosage is 150 to 200 mg/kg/day IV or IM divided every 3 to 4 hours.

For the treatment of severe infections, including bacteremia:
Intravenous or Intramuscular dosage:
Neonates 34 weeks gestation and younger and 0 to 7 days: 50 mg/kg/dose IV or IM every 12 hours.
Neonates 34 weeks gestation and younger and older than 7 days: 75 mg/kg/dose IV or IM every 12 hours.
Neonates older than 34 weeks gestation: 50 mg/kg/dose IV or IM every 8 hours.
Infants, Children, and Adolescents: 50 to 200 mg/kg/day (Max: 8 g/day) IV or IM divided every 6 hours. The FDA-approved dosage is 150 to 200 mg/kg/day IV or IM divided every 3 to 4 hours.

For the treatment of infective endocarditis:
Intravenous or Intramuscular dosage:
Neonates 34 weeks gestation and younger and 0 to 7 days: 50 mg/kg/dose IV or IM every 12 hours.
Neonates 34 weeks gestation and younger and older than 7 days: 75 mg/kg/dose IV or IM every 12 hours.
Neonates older than 34 weeks gestation: 50 mg/kg/dose IV or IM every 8 hours.
Infants: 300 to 400 mg/kg/day IV or IM divided every 4 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved labeling recommends 150 to 200 mg/kg/day IV or IM divided every 3 to 4 hours.
Children and Adolescents: 200 to 400 mg/kg/day IV or IM divided every 4 to 6 hours (Max: 12 g/day) is recommended by guidelines. Ampicillin is recommended as an alternative to penicillin in the setting of penicillin unavailability for streptococcal endocarditis; treat for 4 weeks for native valve endocarditis (NVE) and for 6 weeks for prosthetic valve endocarditis (PVE). Use in combination with gentamicin for streptococcal PVE; duration of concurrent gentamicin (2 or 6 weeks) depends on susceptibility and/or organism. Ampicillin in combination with gentamicin is recommended as preferred therapy for enterococcal infections; treat for 4 to 6 weeks, with a longer course for PVE. Alternately, may use in combination with ceftriaxone in aminoglycoside-resistant enterococcal infection or aminoglycoside-intolerant patient. Ampicillin plus an aminoglycoside for 4 weeks is recommended as an alternate therapy for endocarditis due to HACEK microorganisms. The FDA-approved labeling recommends 150 to 200 mg/kg/day IV or IM divided every 3 to 4 hours.

For bacterial endocarditis prophylaxis*:
Intravenous or Intramuscular dosage:
Children and Adolescents: 50 mg/kg/dose (Max: 2 g/dose) IV or IM as a single dose given 30 to 60 minutes before procedure as an alternative for patients unable to take oral medication. Prophylaxis is recommended for at-risk cardiac patients who are undergoing dental procedures that involve manipulation of gingival tissue, manipulation of the periapical region of teeth, or perforation of the oral mucosa.

For the treatment of upper respiratory tract infections (URTIs) and lower respiratory tract infections (LRTIs), including community-acquired pneumonia (CAP):
-for the treatment of nonspecific respiratory tract infections (RTIs):
Oral dosage:
Infants, Children, and Adolescents: 50 to 100 mg/kg/day (Max: 2 g/day) PO in 4 divided doses. The FDA-approved dosage is 50 mg/kg/day PO in 3 to 4 divided doses (Max: 1 g/day).
Intravenous or Intramuscular dosage:
Neonates 34 weeks gestation and younger and 0 to 7 days*: 50 mg/kg/dose IV or IM every 12 hours.
Neonates 34 weeks gestation and younger and older than 7 days*: 75 mg/kg/dose IV or IM every 12 hours.
Neonates older than 34 weeks gestation*: 50 mg/kg/dose IV or IM every 8 hours.
Infants, Children, and Adolescents: 50 to 200 mg/kg/day (Max: 8 g/day) IV or IM divided every 6 hours. The FDA-approved dosage is 25 to 50 mg/kg/day (Max: 2 g/day) IV or IM divided every 6 to 8 hours.
-for the empiric treatment of community-acquired pneumonia (CAP):
Intravenous or Intramuscular dosage:
Infants, Children, and Adolescents: 150 to 200 mg/kg/day (Max: 8 g/day) IV or IM divided every 6 hours for 5 to 7 days.
-for the treatment of CAP in pediatric patients due to S. pneumoniae (penicillin MIC 2 mcg/mL or less):
Intravenous or Intramuscular dosage:
Infants, Children, and Adolescents: 150 to 200 mg/kg/day (Max: 8 g/day) IV or IM divided every 6 hours for 5 to 7 days.
-for the treatment of CAP in pediatric patients due to S. pneumoniae, relatively resistant (penicillin MIC 4 mcg/mL or more):
Intravenous or Intramuscular dosage:
Infants, Children, and Adolescents: 300 to 400 mg/kg/day (Max: 12 g/day) IV or IM divided every 6 hours for 5 to 7 days.
-for the treatment of CAP in pediatric patients due to Group A Streptococcus:
Intravenous or Intramuscular dosage:
Infants, Children, and Adolescents: 200 mg/kg/day (Max: 8 g/day) IV or IM divided every 6 hours for 5 to 7 days.
-for the treatment of CAP in pediatric patients due to H. influenzae (beta-lactamase negative):
Intravenous or Intramuscular dosage:
Infants, Children, and Adolescents: 150 to 200 mg/kg/day (Max: 8 g/day) IV or IM divided every 6 hours for 5 to 7 days.

For the treatment of skin and skin structure infections (e.g., cellulitis):
Intravenous or Intramuscular dosage:
Neonates 34 weeks gestation and younger and 0 to 7 days*: 50 mg/kg/dose IV or IM every 12 hours.
Neonates 34 weeks gestation and younger and older than 7 days*: 75 mg/kg/dose IV or IM every 12 hours.
Neonates older than 34 weeks gestation*: 50 mg/kg/dose IV or IM every 8 hours.
Infants, Children, and Adolescents: 50 to 200 mg/kg/day (Max: 8 g/day) IV or IM divided every 6 hours. The FDA-approved dosage is 25 to 50 mg/kg/day IV/IM divided every 6 to 8 hours (Max: 2 g/day).

For the treatment of urinary tract infection (UTI):
Oral dosage:
Infants, Children, and Adolescents: 100 mg/kg/day (Max: 2 g/day) PO in 4 divided doses.
Intravenous or Intramuscular dosage:
Neonates 34 weeks gestation and younger and 0 to 7 days*: 50 mg/kg/dose IV or IM every 12 hours.
Neonates 34 weeks gestation and younger and older than 7 days*: 75 mg/kg/dose IV or IM every 12 hours.
Neonates older than 34 weeks gestation*: 50 mg/kg/dose IV or IM every 8 hours.
Infants, Children, and Adolescents: 50 to 200 mg/kg/day (Max: 8 g/day) IV or IM divided every 6 hours. The FDA-approved dosage is 50 mg/kg/day (Max: 2 g/day) IV or IM divided every 6 to 8 hours.

For the treatment of gastrointestinal infections (e.g., enterocolitis, gastroenteritis), including dysentery/shigellosis, salmonellosis, and typhoid fever:
-for the treatment of general gastrointestinal infections, including dysentery/shigellosis and salmonellosis:
Oral dosage:
Infants, Children, and Adolescents: 100 mg/kg/day (Max: 2 g/day) PO divided every 6 hours.
Intravenous or Intramuscular dosage:
Neonates 34 weeks gestation and younger and 0 to 7 days*: 50 mg/kg/dose IV or IM every 12 hours.
Neonates 34 weeks gestation and younger and older than 7 days*: 75 mg/kg/dose IV or IM every 12 hours.
Neonates older than 34 weeks gestation*: 50 mg/kg/dose IV or IM every 8 hours.
Infants, Children, and Adolescents: 50 to 200 mg/kg/day (Max: 8 g/day) IV or IM divided every 6 hours. The FDA-approved dosage is 50 mg/kg/day (Max: 2 g/day) IV or IM divided every 6 to 8 hours.
-for the treatment of fully sensitive uncomplicated typhoid fever:
Oral dosage:
Infants, Children, and Adolescents: 50 to 100 mg/kg/day PO divided every 6 to 8 hours (Max: 500 mg/dose) for 14 days as an alternative.
-for the treatment of fully sensitive severe typhoid fever:
Intravenous or Intramuscular dosage:
Infants, Children, and Adolescents: 100 to 200 mg/kg/day IV or IM divided every 6 to 8 hours (Max: 2 g/dose) for 14 days as an alternative.

For the treatment of intraabdominal infections*, including peritonitis*, appendicitis*, intraabdominal abscess*, neonatal necrotizing enterocolitis*, and peritoneal dialysis-related peritonitis*:
-for the treatment of complicated community-acquired, healthcare-acquired, or hospital-acquired intraabdominal infections* with adequate source control:
Intravenous dosage:
Neonates 34 weeks gestation and younger and 0 to 7 days: 50 mg/kg/dose IV every 12 hours as part of combination therapy for 7 to 10 days. Ampicillin is an option for necrotizing enterocolitis.
Neonates 34 weeks gestation and younger and older than 7 days: 75 mg/kg/dose IV every 12 hours as part of combination therapy for 7 to 10 days. Ampicillin is an option for necrotizing enterocolitis.
Neonates older than 34 weeks gestation: 50 mg/kg/dose IV every 8 hours as part of combination therapy for 7 to 10 days. Ampicillin is an option for necrotizing enterocolitis.
Infants, Children, and Adolescents: 100 to 200 mg/kg/day (Max: 8 g/day) IV divided every 6 hours as part of combination therapy for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.
-for the treatment of uncomplicated intraabdominal infections*:
Intravenous dosage:
Infants, Children, and Adolescents: 100 to 200 mg/kg/day (Max: 8 g/day) IV divided every 6 hours part of combination therapy. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.
-for the treatment of peritoneal dialysis-related peritonitis*:
Continuous Intraperitoneal dosage*:
Infants, Children, and Adolescents: 125 mg/L in each dialysate exchange. Treat for 14 to 21 days.

For surgical infection prophylaxis* in patients undergoing liver transplantation:
Intravenous or Intramuscular dosage:
Infants, Children, and Adolescents: 50 mg/kg IV or IM as a single dose (Max: 2 g/dose) within 60 minutes prior to the surgical incision, in combination with cefotaxime. Intraoperative redosing 2 hours from the first preoperative dose and a duration of prophylaxis less than 24 hours are recommended by clinical practice guidelines.

For the treatment of anthrax*:
-for the treatment of cutaneous anthrax* without aerosol exposure or signs and symptoms of meningitis:
Oral dosage:
Infants, Children, and Adolescents: 25 mg/kg/dose (Max: 500 mg/dose) PO every 6 hours for 7 to 10 days or until clinical criteria for stability are met.
-for the treatment of cutaneous anthrax* with aerosol exposure and without signs and symptoms of meningitis:
Oral dosage:
Infants, Children, and Adolescents: 25 mg/kg/dose (Max: 500 mg/dose) PO every 6 hours for 7 to 10 days or until clinical criteria for stability are met and then transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course.
-for the treatment of systemic anthrax* without aerosol exposure, including those with signs and symptoms of meningitis, as part of combination therapy:
Intravenous or Intramuscular dosage:
Neonates 32 to 33 weeks gestation and 0 to 6 days: 50 mg/kg/dose IV or IM every 12 hours for at least 14 days; may consider step-down to oral therapy.
Neonates 32 to 33 weeks gestation and 7 days and older: 75 mg/kg/dose IV or IM every 12 hours for at least 14 days; may consider step-down to oral therapy.
Neonates 34 weeks gestation and older: 50 mg/kg/dose IV or IM every 8 hours for at least 14 days; may consider step-down to oral therapy.
Infants, Children, and Adolescents: 50 mg/kg/dose (Max: 3 g/dose) IV every 6 hours for at least 14 days; may consider step-down to oral therapy.
-for the treatment of systemic anthrax* with aerosol exposure, including those with signs and symptoms of meningitis, as part of combination therapy:
Intravenous or Intramuscular dosage:
Neonates 32 to 33 weeks gestation and 0 to 6 days: 50 mg/kg/dose IV or IM every 12 hours for at least 14 days; may consider step-down to oral therapy. Transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course from illness onset.
Neonates 32 to 33 weeks gestation and 7 days and older: 75 mg/kg/dose IV or IM every 12 hours for at least 14 days; may consider step-down to oral therapy. Transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course from illness onset.
Neonates 34 weeks gestation and older: 50 mg/kg/dose IV or IM every 8 hours for at least 14 days; may consider step-down to oral therapy. Transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course from illness onset.
Infants, Children, and Adolescents: 50 mg/kg/dose (Max: 3 g/dose) IV every 6 hours for at least 14 days; may consider step-down to oral therapy.
Immunocompromised Infants, Children, and Adolescents: 50 mg/kg/dose (Max: 3 g/dose) IV every 6 hours for at least 14 days; may consider step-down to oral therapy. Transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course from illness onset.

For chronic typhoid carriage eradication*:
Oral dosage:
Infants, Children, and Adolescents: 100 mg/kg/day PO divided every 6 to 8 hours plus probenecid for 4 to 6 weeks.

For the treatment of leptospirosis*:
Oral dosage:
Infants, Children, and Adolescents: 50 to 100 mg/kg/day (Max: 2 g/day) PO divided every 6 hours for 7 to 10 days as alternative therapy for mild or moderate disease.

For the treatment of listeriosis*:
NOTE: For CNS disease, see meningitis indication.
-for the treatment of invasive listeriosis* with bacteremia:
Intravenous dosage:
Neonates 0 to 7 days: 100 mg/kg/dose IV every 8 hours for 14 days; consider the addition of gentamicin.
Neonates older than 7 days: 75 mg/kg/dose IV every 6 hours for 14 days; consider the addition of gentamicin.
Infants, Children, and Adolescents: 100 to 400 mg/kg/day (Max: 12 g/day) IV divided every 4 to 6 hours for 14 days; consider the addition of gentamicin.
-for the treatment of gastroenteritis due L. monocytogenes* in persons at risk for invasive disease:
Oral dosage:
Infants, Children, and Adolescents: 100 mg/kg/day (Max: 2 g/day) PO divided every 6 hours for 3 to 7 days.

For the treatment of rat-bite fever* as step-down therapy:
Oral dosage:
Infants, Children, and Adolescents: 50 to 100 mg/kg/day (Max: 2 g/day) PO divided every 6 hours for 7 days after an initial treatment course with intravenous penicillin G.

Maximum Dosage Limits:
-Neonates
0 to 7 days and 34 weeks gestation or younger: 100 mg/kg/day IV/IM per FDA-approved product labeling; however, doses up to 300 mg/kg/day IV have been used off-label for serious infections.
0 to 7 days and older than 34 weeks gestation : 150 mg/kg/day IV/IM per FDA-approved product labeling; however, doses up to 300 mg/kg/day IV have been used off-label for serious infections.
older than 7 days: 150 mg/kg/day IV/IM per FDA-approved product labeling; however, doses up to 300 mg/kg/day IV have been used off-label for serious infections.
-Infants
100 mg/kg/day PO; 200 mg/kg/day IV/IM per FDA-approved product labeling; however, doses up to 400 mg/kg/day IV have been used off-label for serious infections.
-Children
100 mg/kg/day PO (Max: 2 g/day); 200 mg/kg/day IV/IM per FDA-approved product labeling; however, doses up to 400 mg/kg/day IV (Max: 12 g/day) have been used off-label for serious infections.
-Adolescents
100 mg/kg/day PO (Max: 2 g/day); 200 mg/kg/day IV/IM per FDA-approved product labeling; however, doses up to 400 mg/kg/day IV (Max: 12 g/day) have been used off-label for serious infections.

Patients with Hepatic Impairment Dosing
No dosage adjustment is needed.

Patients with Renal Impairment Dosing
The following dosage adjustments are recommendations based on a usual dose of 100 to 200 mg/kg/day IV divided every 6 hours.
GFR 30 mL/minute/1.73 m2 or more: No dosage adjustment needed.
GFR 10 to 29 mL/minute/1.73 m2: Extend dosing interval to every 8 to 12 hours.
GFR less than 10 mL/minute/1.73 m2: Extend dosing interval to every 12 hours.

Intermittent hemodialysis
Ampicillin is significantly removed during a standard hemodialysis session; give recommended dose every 12 hours after dialysis.

Peritoneal dialysis
Extend dosing interval to every 12 hours.

Continuous renal replacement therapy (CRRT)
Give recommended dose every 6 hours.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Beta-lactam antibiotics, such as ampicillin, are mainly bactericidal. Like other penicillins, ampicillin inhibits the third and final stage of bacterial cell wall synthesis by preferentially binding to specific penicillin-binding proteins (PBPs) that are located inside the bacterial cell wall. Penicillin-binding proteins are responsible for several steps in the synthesis of the cell wall and are found in quantities of several hundred to several thousand molecules per bacterial cell. Penicillin-binding proteins vary among different bacterial species. Thus, the intrinsic activity of ampicillin, as well as the other penicillins, against a particular organism depends on their ability to gain access to and bind with the necessary PBP. Like all beta-lactam antibiotics, ampicillin's ability to interfere with PBP-mediated cell wall synthesis ultimately leads to cell lysis. Lysis is mediated by bacterial cell wall autolytic enzymes (i.e., autolysins). The relationship between PBPs and autolysins is unclear, but it is possible that the beta-lactam antibiotic interferes with an autolysin inhibitor. Prevention of the autolysin response to beta-lactam antibiotic exposure through loss of autolytic activity (mutation) or inactivation of autolysin (low-medium pH) by the microorganism can lead to tolerance to the beta-lactam antibiotic resulting in bacteriostatic activity.

The susceptibility interpretive criteria for ampicillin are delineated by pathogen. The MICs are defined for Enterobacterales and Vibrio sp. as susceptible at 8 mcg/mL or less, intermediate at 16 mcg/mL, and resistant at 32 mcg/mL or more (based on a dosage regimen of 2 g IV/IM every 4 to 6 hours, or 500 mg PO every 6 hours for salmonellosis, shigellosis, or uncomplicated urinary tract infection (UTI) due to E. coli and P. mirabilis). The MICs are defined for Enterococcus sp. as susceptible at 8 mcg/mL or less and resistant at 16 mcg/mL or more (based on a dosage regimen of 2 g IV/IM every 4 to 6 hours, or 500 mg PO every 6 hours for uncomplicated UTI). The MICs are defined for H. influenzae, H. parainfluenzae, Aggregatibacter sp., Cardiobacterium sp., E. corrodens, Kingella sp., and Lactococcus sp. as susceptible at 1 mcg/mL or less, intermediate at 2 mcg/mL, and resistant at 4 mcg/mL or more. H. influenzae and H. parainfluenzae breakpoints when used for meningitis are based on a dosage regimen of 2 g IV/IM every 4 hours. The MICs are defined for Streptococcus sp. beta-hemolytic group and E. rhusiopathiae as susceptible at 0.25 mcg/mL or less. The MICs are defined for Streptococcus sp. viridans group, Abiotrophia sp., and Granulicatella sp. as susceptible at 0.25 mcg/mL or less, intermediate at 0.5 to 4 mcg/mL, and resistant at 8 mcg/mL or more. Non-meningitis S. pneumoniae that are susceptible to penicillin are predictably sensitive to ampicillin. The MICs are defined for N. meningitidis as susceptible at 0.12 mcg/mL or less, intermediate at 0.25 to 1 mcg/mL, and resistant at 2 mcg/mL or more (based on a dosage regimen of 2 g IV/IM every 4 hours). The MICs are defined for anaerobes as susceptible at 0.5 mcg/mL or less, intermediate at 1 mcg/mL, and resistant at 2 mcg/mL or more. The MIC are defined for L. monocytogenes as susceptible at 2 mcg/mL or less. The MICs are defined for Lactobacillus sp., Leuconostoc sp., and Pediococcus sp. as susceptible at 8 mcg/mL or less. The MICs are defined for Pasteurella sp. as susceptible at 0.5 mcg/mL or less. The MICs are defined for Bacillus sp. (excluding B. anthracis) and related genera as susceptible at 0.25 mcg/mL or less and resistant at 0.5 mcg/mL or more.

Pharmacokinetics: Ampicillin is administered orally and parenterally by intravenous or intramuscular routes. Ampicillin is the least serum-bound of all the penicillins, averaging roughly 20% compared to approximately 60-90% for other penicillins. The drug is widely distributed into most body tissues and fluid; concentrations of the active drug are higher in bile than in the serum. Therapeutic concentrations are attained within the CSF only in the presence of meningeal inflammation. The drug crosses the placenta, and a small percentage is excreted in breast milk. Ampicillin is primarily eliminated in the urine as unchanged drug. In infants and children with normal renal function, the elimination half-life of ampicillin is approximately 1-1.6 hours.

Affected cytochrome P450 isoenzymes: none


-Route-Specific Pharmacokinetics
Oral Route
Peak concentrations achieved 1 hour after administration.

Intravenous Route
Peak concentrations occur almost immediately after a 15-minute intravenous (IV) infusion.


-Special Populations
Pediatrics
Neonates
The elimination half-life of ampicillin in preterm and term neonates is approximately 3-4 hours in the first week of life and decreases to approximately 2-3 hours at 7 days postnatal age. At approximately 30 days postnatal age, the elimination half-life is approximately 1.6 hours, which is similar to infants and children.

Infants, Children, and Adolescents
The elimination half-life is approximately 1-1.6 hours.

Renal Impairment
Data are unavailable in pediatric patients. The elimination half-life in adults with end-stage renal disease has been reported to be approximately 7-20 hours.