section name header

Introduction

VA Class:AM111

AHFS Class:

Generic Name(s):

Chemical Name:

Molecular Formula:

Associated Monographs

Ampicillin is an aminopenicillin antibiotic.64,76,77

Uses

Ampicillin shares the uses of other aminopenicillins and is used principally for the treatment of infections caused by susceptible gram-negative bacteria (e.g., Haemophilus influenzae , Escherichia coli , Proteus mirabilis , Salmonella ).38,39,42,45,46,48,49,67,741,917,1098 Ampicillin also is used for the treatment of infections caused by susceptible gram-positive bacteria (e.g., Streptococcus pneumoniae , enterococci, nonpenicillinase-producing staphylococci, Listeria );38,39,42,45,46,48,49,67,864,2337 however, like other aminopenicillins, ampicillin generally should not be used for the treatment of streptococcal or staphylococcal infections when a natural penicillin would be effective.63,64,67,80,864,869,904,906,2337 Orally administered ampicillin should not be used for the initial treatment of severe, life-threatening infections, but may be used as follow-up therapy after parenteral ampicillin therapy.64,904,906 For specific information on the uses of ampicillin, see Uses in the Aminopenicillins General Statement 8:12.16.08.

Dosage and Administration

[Section Outline]

Reconstitution and Administration !!navigator!!

Ampicillin trihydrate is administered orally.42,45,46,48,49,1420 Although ampicillin may be given orally with meals, maximum absorption is achieved when the drug is administered 1 hour before or 2 hours after meals.

Ampicillin sodium may be administered by IM or slow IV injection or by IV infusion.38,39

Parenteral forms of ampicillin should be used only in the treatment of moderately severe or severe infections. Direct IV injections should be made slowly over 10-15 minutes to avoid the possibility of seizures.38,39 For intermittent IV infusion, the concentration of ampicillin and rate of infusion should be adjusted so that the total dose of the drug is administered before 10% or more of the drug is inactivated in the IV solution.38 (See Chemistry and Stability: Stability.)

Ampicillin sodium preparations for parenteral use should be reconstituted according to the manufacturers' instructions.38,39 Ampicillin sodium solutions should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Dosage !!navigator!!

Dosage of ampicillin sodium and ampicillin trihydrate is expressed in terms of ampicillin.38,39,42,45,46,48,49

The manufacturers' dosage recommendations for adults usually are the same for both parenteral and oral routes;38,39,42,45,46,48,49 however, higher serum concentrations usually are attained parenterally,67,338,404,453 and this route is used for severe infections.64,904,906

General Adult Dosage

The usual adult dosage of ampicillin for the treatment of respiratory tract or skin and skin structure infections is 250-500 mg every 6 hours.38,39,42,46,48,49 For the treatment of GI or urinary tract infections, the usual adult dosage is 500 mg every 6 hours.38,39,42,46,48,49 For severe infections, larger doses may be required.38,39,42,46,48,49

The usual adult dosage of ampicillin for the treatment of septicemia or bacterial meningitis is 8-14 g or 150-200 mg/kg daily given parenterally in equally divided doses every 3-4 hours.38,39 For the initial treatment of septicemia or meningitis, ampicillin should be given IV for at least 3 days but may then be given IM.38,39

General Pediatric Dosage

For oral therapy, most manufacturers state that children weighing more than 20 kg may receive the usual adult dosage of ampicillin.42,48,49 For parenteral therapy, some manufacturers recommend that the usual adult dosage be used in children weighing more than 20 kg, whereas other manufacturers and many clinicians recommend that the usual adult dosage be used in those weighing more than 40 kg.38,39,1413,1415 Pediatric dosage should not exceed dosage recommended for similar infections in adults.38,39

For the treatment of respiratory tract or skin and skin structure infections, the usual dosage of ampicillin for children weighing 40 kg or less is 25-50 mg/kg daily administered in equally divided doses every 6 hours.38,39,42,45,46,48,49 For the treatment of GI or urinary tract infections, the usual dosage for children weighing 40 kg or less is 50-100 mg/kg daily given in equally divided doses every 6 hours.38,39,42,45,46,48,49

For the treatment of septicemia or CNS infections, the usual pediatric dosage recommended by the manufacturers is 100-200 mg/kg daily given in divided doses every 3-4 hours, starting with IV administration for 3 days and continuing with IM administration.38,39 For empiric treatment of bacterial meningitis in neonates and children younger than 2 months of age, many clinicians recommend that an IV ampicillin dosage of 100-300 mg/kg daily be given in divided doses in conjunction with IM gentamicin pending results of in vitro susceptibility tests.866,986,1414,1423,1647 For the empiric treatment of bacterial meningitis in children 2 months to 12 years of age, many clinicians recommend that an IV ampicillin dosage of 200-400 mg/kg daily be given in divided doses every 4-6 hours in conjunction with IV chloramphenicol.866,986,1414,1647 If bacterial susceptibility data are not available and clinical and bacteriologic response is unsatisfactory after 24-48 hours, other appropriate anti-infective therapy should be substituted.986,1414

When IM or IV ampicillin is used in neonates younger than 7 days of age, the American Academy of Pediatrics (AAP) recommends a dosage of 50 mg/kg every 12 hours in those weighing 2 kg or less or 50 mg/kg every 8 hours in those weighing more than 2 kg.292 For neonates 8-28 days of age, AAP recommends an IM or IV dosage of 50 mg/kg every 8 hours in those weighing 2 kg or less or 50 mg/kg every 6 hours in those weighing more than 2 kg.292 AAP states that higher ampicillin dosage may be necessary for the treatment of meningitis in neonates.292 For the treatment of meningitis caused by Streptococcus agalactiae (group B streptococci; GBS), some experts recommend that neonates 28 days of age or younger receive IV ampicillin in a dosage of 75 mg/kg every 6 hours, regardless of weight;292 others recommend a dosage of 200-300 mg/kg daily given IV in 3 divided doses in neonates 7 days of age or younger or a dosage of 300 mg/kg daily given IV in 4 divided doses in neonates older than 7 days of age.292 AAP states that a dosage of 100 mg/kg every 12 hours is acceptable for the treatment of early-onset group B streptococcal septicemia without meningitis in neonates 7 days of age or younger.292

When IM or IV ampicillin is used in pediatric patients beyond the neonatal period, AAP recommends a dosage of 100-150 mg/kg daily given in 4 divided doses for the treatment of mild to moderate infections or a dosage of 200-400 mg/kg daily given in 4 divided doses for the treatment of severe infections.292 The highest dosage should be used for the treatment of CNS infections.292 When oral ampicillin is used in pediatric patients beyond the neonatal period, AAP recommends a dosage of 50-100 mg/kg daily in 4 divided doses.292 AAP states that oral ampicillin is inappropriate for the treatment of severe infections.292

Treatment of Enterococcal Endocarditis

If IV ampicillin is used for the treatment of enterococcal endocarditis, the American Heart Association (AHA) and others recommend that adults receive 2 g every 4 hours in conjunction with gentamicin.450 Treatment with both drugs generally should be continued for 4-6 weeks, but patients who had symptoms of infection for more than 3 months before treatment was initiated and patients with prosthetic heart valves require a minimum of 6 weeks of therapy with both drugs.450

Prevention of Perinatal Group B Streptococcal Disease

If IV ampicillin is used as an alternative to IV penicillin G for intrapartum anti-infective prophylaxis for prevention of early-onset neonatal group B streptococcal (GBS) disease (see Prevention of Perinatal Group B Streptococcal Disease under Uses in the Aminopenicillins General Statement 8:12.16.08), the American College of Obstetricians and Gynecologists (ACOG), AAP, and other experts recommend an initial IV ampicillin loading dose of 2 g at the onset of labor or rupture of membranes followed by 1 g IV every 4 hours until delivery.292,359

Regardless of whether anti-infective prophylaxis was administered to the mother, appropriate diagnostic evaluations and anti-infective therapy should be initiated in the neonate if signs or symptoms of active infection develop.292,359

Prevention of Bacterial Endocarditis

If IM or IV ampicillin is used for prevention of bacterial endocarditis in patients with certain cardiac conditions who are undergoing certain dental procedures or certain other procedures who cannot receive an oral regimen (see Prevention of Bacterial Endocarditis under Uses in the Aminopenicillins General Statement 8:12.16.08), AHA recommends that adults receive a single 2-g dose and that children receive a single 50-mg/kg dose of the drug given 30-60 minutes prior to the procedure.451

When selecting anti-infectives for prevention of bacterial endocarditis, the current recommendations published by AHA should be consulted.451

Duration of Therapy

The duration of ampicillin therapy depends on the type and severity of infection and should be determined by the clinical and bacteriologic response of the patient.38,39,42,45,46,48,49 For most infections, except gonorrhea, therapy should be continued for at least 48-72 hours after the patient becomes asymptomatic or evidence of eradication of the infection has been obtained.38,39,42,45,46,48,49 Persistent infections may require several weeks of therapy.38,39,42,45,46,48,49

Dosage in Renal Impairment !!navigator!!

In patients with renal impairment, doses and/or frequency of administration of ampicillin should be modified in response to the degree of renal impairment, severity of the infection, and susceptibility of the causative organism.510,1320,1373,1374 Some clinicians suggest that adults with glomerular filtration rates of 10-50 mL/minute receive the usual dose of ampicillin every 6-12 hours and that adults with glomerular filtration rates less than 10 mL/minute receive the usual dose every 12-16 hours.1373 Alternatively, some clinicians suggest that modification of usual dosage of ampicillin is unnecessary in adults with creatinine clearances of 30 mL/minute or greater, but adults with creatinine clearances of 10 mL/minute or less should receive the usual dose of the drug every 8 hours.1320

Patients undergoing hemodialysis should receive a supplemental dose of ampicillin after each dialysis period.1319,1320,1373

Cautions

[Section Outline]

Adverse Effects !!navigator!!

Adverse effects reported with ampicillin are similar to those reported with other aminopenicillins;38,39,42,45,46,48,49 however, diarrhea725,727,731,732,741,747,502,583 and rash61,73,614,732,812 have been reported more frequently with ampicillin than with other currently available aminopenicillins. For information on adverse effects reported with aminopenicillins, see Cautions in the Aminopenicillins General Statement 8:12.16.08.

Precautions and Contraindications !!navigator!!

Ampicillin shares the toxic potentials of the penicillins, including the risk of hypersensitivity reactions, and the usual precautions of penicillin therapy should be observed.38,39,42,45,46,48,49,1420 Prior to initiation of therapy with ampicillin careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, or other drugs.38,39,42,45,46,48,49,1420 There is clinical and laboratory evidence of partial cross-allergenicity among penicillins and other β-lactam antibiotics including cephalosporins, cephamycins, and 1-oxa-β-lactams.611,615,720,769,781,1193 Ampicillin is contraindicated in patients who are hypersensitive to any penicillin.38,39,42,45,46,48,49,1420

Because a high percentage of patients with infectious mononucleosis have developed rash during therapy with aminopenicillins, ampicillin probably should not be used in patients with this disease.73,428

Renal, hepatic, and hematologic systems should be evaluated periodically during prolonged therapy with ampicillin.38,39,42,45,46,48,49,1420

For a more complete discussion of these and other precautions associated with the use of ampicillin, see Cautions: Precautions and Contraindications, in the Aminopenicillins General Statement 8:12.16.08.

Pregnancy and Lactation !!navigator!!

Pregnancy

Safe use of ampicillin during pregnancy has not been established.38,39,42,45,46,48,49,1420 There are no adequate or controlled studies using ampicillin in pregnant women, and the drug should be used during pregnancy only when clearly needed. However, ampicillin has been administered to pregnant women, especially in the treatment of urinary tract infections, without evidence of adverse effects to the fetus.61,468,723,1145

Lactation

Because ampicillin is distributed into milk, the drug should be used with caution in nursing women.61,73,355

Other Information

[Section Outline]

Spectrum

Based on its spectrum of activity, ampicillin is classified as an aminopenicillin.62,76,88,575 For information on the classification of penicillins based on spectra of activity, see the Preface to the Penicillins 8:12.16.

Ampicillin generally has the same spectrum of activity and the same level of activity against susceptible organisms as amoxicillin;61,64,68,73,75,226,228,229,575 however, ampicillin is less active in vitro on a weight basis than amoxicillin against enterococci and Salmonella but more active than amoxicillin against Shigella and Enterobacter .73,149,150,151,228,229,329,1314 For specific information on in vitro susceptibility testing and information on the spectrum of activity of ampicillin and resistance to the drug, see the sections on Spectrum and on Resistance in the Aminopenicillins General Statement 8:12.16.08.

Pharmacokinetics

For additional information on absorption and distribution of ampicillin and information on elimination of the drug, see Pharmacokinetics in the Aminopenicillins General Statement 8:12.16.08.

Absorption !!navigator!!

Ampicillin trihydrate generally are stable in the presence of acidic gastric secretions,42,45,46,48,49,64,68,81,341 and 30-55% of an oral dose of the drugs is absorbed from the GI tract in fasting adults.63,67,81,320,341,366,494,487 Although peak serum concentrations may occur as soon as 1 hour after administration, the maximum serum concentration usually is attained in approximately 2 hours.68,81,443,460,502,512 Two hours after oral administration of 250 mg of ampicillin in fasting individuals, average peak serum concentrations of 1.8-2.9 mcg/mL are attained.428,478 A 500-mg oral dose results in average peak serum concentrations of 3-6 mcg/mL.428,479 Concentrations of the antibiotic in serum are less than 1 mcg/mL 6 hours after a 500-mg oral dose.428,479 Although higher peak serum ampicillin concentrations and larger areas under the serum concentration-time curves (AUCs) have been reported following oral administration of anhydrous ampicillin than following the trihydrate,1431,1432 the differences are generally not considered clinically important. As oral dosage of ampicillin is increased from 500 mg to 2 g, the fraction of the dose absorbed from the GI tract decreases and, there is a nonlinear relationship between dosage and peak serum concentrations or AUCs of ampicillin.433

Presence of food in the GI tract generally decreases the rate and extent of absorption of ampicillin.342,457,466

Following IM administration of ampicillin sodium, peak serum concentrations generally are attained more quickly and are higher than those resulting from equivalent doses of ampicillin given orally.67,338,404,453 In premature neonates younger than 7 days of age, IM administration of a single ampicillin dose of 50 mg/kg has been reported to produce mean serum concentrations of 104, 87, 60, and 31 mcg/mL at 1, 4, 8, and 12 hours, respectively, after the dose.1423 The same dose in full-term neonates younger than 7 days of age produced mean serum concentrations of 75, 64, 34, and 20 mcg/mL at the same time intervals.1423

Following IV administration over 20 minutes of a single 2-g dose of ampicillin in healthy adults, serum concentrations of ampicillin averaged 47.6, 23.3, 10.8, and 3.7 mcg/mL at 30 minutes, 1 hour, 2 hours, and 4 hours, respectively, after the infusion.338

Serum ampicillin concentrations are higher and the serum half-life is prolonged in patients with impaired renal function.320,328,348 Serum concentrations of the drug also are higher and more prolonged in premature or full-term neonates younger than 6 days of age than in full-term neonates 6 days of age or older.340,358,470,484

Distribution !!navigator!!

In one study in neonates with meningitis, average ampicillin concentrations in CSF ranged from 1-28 mcg/mL (11-65% of simultaneous serum concentrations) during the 7-hour period following IV administration of 40-70 mg/kg.1423 Highest CSF concentrations occurred at 3-7 hours.1423

Ampicillin is distributed into bile.67,68,72,320 Biliary concentrations of ampicillin in patients with normal biliary function may be 1-30 times greater than simultaneous serum concentrations following a single oral dose of ampicillin.61,72,320

Chemistry and Stability

Chemistry !!navigator!!

Ampicillin is an aminopenicillin.64,76,77 Ampicillin differs structurally from penicillin G only in the presence of an amino group at the α-position on the benzene ring at R on the penicillin nucleus.88

Ampicillin is commercially available as ampicillin trihydrate for oral administration and as the sodium salt for parenteral administration.1,38,39,42,45,46,48,49 Potency of ampicillin trihydrate and ampicillin sodium is expressed in terms of ampicillin and is calculated on the anhydrous basis.1,38,39,42,45,46,48,49

Ampicillin trihydrate occurs as a white, practically odorless, crystalline powder that is slightly soluble in water.1 Ampicillin trihydrate reportedly has aqueous solubility of about 6 mg/mL at 20°C and about 10 mg/mL at 40°C.1431 Ampicillin sodium occurs as a white to off-white, odorless or practically odorless, crystalline, hygroscopic powder and is very soluble in water, in 0.9% sodium chloride, and in dextrose solutions.1 Reconstituted solutions of ampicillin sodium containing 10 mg of ampicillin per mL have a pH of 8-10.1 When reconstituted as directed, ampicillin trihydrate oral suspensions have a pH of 5-7.5.1

Commercially available ampicillin sodium powder for injection contains 2.9-3.1 mEq of sodium per g of ampicillin.38,39

Stability !!navigator!!

Ampicillin capsules and powder for oral suspension should be stored in tight containers at 15-30°C.1420,1835,1836,1837,1838 Following reconstitution, oral suspension of ampicillin trihydrate preferably should be refrigerated at 2-8°C48,49 but is stable for 7 days at room temperature or 14 days at 2-8°C.48,49

Following reconstitution with sterile or bacteriostatic water for injection, ampicillin sodium solutions for IM or direct IV injection should be used within 1 hour after reconstitution38,39 and should not be frozen.1 The stability of ampicillin sodium in solution is concentration dependent and decreases as the concentration of the drug increases.82 Ampicillin sodium appears to be especially susceptible to inactivation in solutions containing dextrose, which appears to have a catalytic effect on hydrolysis of the drug.82,93

The manufacturers report that when stored at room temperature (25°C), ampicillin sodium solutions containing 30 mg or less of ampicillin per mL in sterile water for injection, 0.9% sodium chloride injection, (1/6) M sodium lactate injection, or lactated Ringer's injection lose less than 10% of activity within 8 hours and solutions containing 2 mg or less of ampicillin per mL in 5% dextrose, 5% dextrose and 0.45% sodium chloride, or 10% invert sugar lose less than 10% of activity within 4 hours.38,39 At concentrations of 10-20 mg/mL in 5% dextrose, ampicillin loses less than 10% of its activity within 2 hours at room temperature.38,39

When refrigerated at 4°C, ampicillin sodium solutions containing 30 mg of ampicillin per mL are stable for 48 hours in sterile water for injection or 0.9% sodium chloride injection and solutions containing 30 mg or less per mL are stable for 24 hours in lactated Ringer's or 8 hours in (1/6) M sodium lactate injection.38,39 Solutions of the drug containing 20 mg or less of ampicillin per mL are stable at 4°C for 72 hours in sterile water for injection or 0.9% sodium chloride injection, 4 hours in 5% dextrose, or 3 hours in 10% invert sugar and solutions containing 10 mg or less per mL are stable for 4 hours at 4°C in 5% dextrose and 0.45% sodium chloride.38,39

Ampicillin sodium is potentially physically and/or chemically incompatible with some drugs, including aminoglycosides, but the compatibility depends on several factors (e.g., concentrations of the drugs, specific diluents used, resulting pH, temperature).38,39,82 For information on the in vitro and in vivo incompatibility of penicillins and aminoglycosides, see Drug Interactions: Aminoglycosides, in the Aminopenicillins General Statement 8:12.16.08. Specialized references should be consulted for specific compatibility information.82 Because of the potential for incompatibility, ampicillin sodium and aminoglycosides should not be admixed.82

Additional Information

For further information on chemistry and stability, mechanism of action, spectrum, resistance, pharmacokinetics, uses, cautions, drug interactions, laboratory test interferences, and dosage and administration of ampicillin, see the Aminopenicillins General Statement 8:12.16.08.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Ampicillin (Trihydrate)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

250 mg (of ampicillin)*

Ampicillin Capsules

500 mg (of ampicillin)*

Ampicillin Capsules

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Ampicillin Sodium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection

125 mg (of ampicillin)*

Ampicillin Sodium for Injection

250 mg (of ampicillin)*

Ampicillin Sodium for Injection

500 mg (of ampicillin)*

Ampicillin Sodium for Injection

1 g (of ampicillin)*

Ampicillin Sodium for Injection

2 g (of ampicillin)*

Ampicillin Sodium for Injection

10 g (of ampicillin) pharmacy bulk package*

Ampicillin Sodium for Injection

For injection, for IV infusion

1 g (of ampicillin)*

Ampicillin Sodium ADD-Vantage®

Ampicillin Sodium Piggyback

2 g (of ampicillin)*

Ampicillin Sodium ADD-Vantage®

Ampicillin Sodium Piggyback

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Copyright

AHFS® Drug Information. © Copyright, 1959-2024, Selected Revisions February 2, 2022. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

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