AMPICILLIN-SULBACTAM (Generic for UNASYN)

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

Route-Specific Administration

Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
-Ampicillin; sulbactam 1.5 grams corresponds to 1 gram of ampicillin plus 0.5 grams of sulbactam. Ampicillin; sulbactam 3 grams corresponds to 2 grams of ampicillin plus 1 gram of sulbactam.
Intravenous Administration
Reconstitution
-Vials: Reconstitute 1.5 g vial with 3.2 ml or 3 g vial with 6.4 ml of sterile water for injection to give a solution containing 375 mg/ml ampicillin; sulbactam (250 mg of ampicillin and 125 mg of sulbactam per ml). Immediately further dilute.
-Pharmacy bulk vial: Reconstitute 15 g vial with 92 ml of sterile water for injection or NS for a resultant concentration of 150 mg/ml ampicillin; sulbactam (100 mg of ampicillin and 50 mg of sulbactam per ml). The diluent should be added in two aliquots; first add 50 ml and shake to dissolve, then add 42 ml and shake. Use contents of pharmacy bulk vial within 2 hours if stored at room temperature and 4 hours if stored under refrigeration.
-Piggyback bottles: Reconstitute with up to 100 ml of a compatible IV solution (i.e., NS, D5W, LR).
-ADD-Vantage vials: For IV infusion only. Reconstitute with NS only using the appropriate ADD-Vantage diluent containers. 1.5 g ADD-Vantage vials should be used with 50 ml, 100 ml, or 250 ml diluent container; 3 g ADD-Vantage vials should be used with 100 ml or 250 ml diluent containers.

Dilution
-Vials: Further dilute vials with compatible IV solution (i.e., NS, D5W, LR) to a usual concentration of 3-45 mg/ml of ampicillin; sulbactam (i.e., 2-30 mg/ml ampicillin and 1-15 mg/ml of sulbactam).
-Piggyback bottles: Following reconstitution, no further dilution is required.
-ADD-Vantage vials: Following reconstitution, no further dilution is required.
-Storage: Diluted solutions are stable for the following time periods in the following diluents :-NS: Stable for 8 hours at room temperature or 48 hours refrigerated at a maximum concentration of 45 mg/ml ampicillin; sulbactam (i.e., 30/15 mg/ml of ampicillin/sulbactam); stable for 72 hours refrigerated at a maximum concentration of 30 mg/ml ampicillin; sulbactam (i.e., 20/10 mg/ml of ampicillin/sulbactam).
-D5W: Stable for 2 hours at room temperature or 4 hours refrigerated at a maximum concentration of 30 mg/ml ampicillin; sulbactam (i.e., 20/10 mg/ml of ampicillin/sulbactam); stable for 4 hours at room temperature at a maximum concentration of 3 mg/ml of ampicillin; sulbactam (i.e., 2/1 mg/ml of ampicillin/sulbactam).
-LR: Stable for 8 hours at room temperature or 24 hours refrigerated at a maximum concentration of 45 mg/ml ampicillin; sulbactam (i.e., 30/15 mg/ml of ampicillin/sulbactam).
-ADD-Vantage vials: Diluted in NS are stable for 8 hours at room temperature at a maximum concentration of 30 mg/ml ampicillin; sulbactam (i.e., 20/10 mg/ml of ampicillin/sulbactam).
-Solutions prepared from reconstituted Pharmacy bulk vials stored for < 1 hour at room temperature: The above storage conditions apply.
-Solutions prepared from reconstituted Pharmacy bulk vials stored for 1-2 hours at room temperature: Solutions diluted in NS are stable for 4 hours at room temperature or 24 hours refrigerated at a maximum concentration of 45 mg/ml ampicillin; sulbactam (i.e., 30/15 mg/ml of ampicillin/sulbactam).


Intermittent IV Infusion
-Infuse via slow IV injection over 10-15 minutes or as an IV infusion over 15-30 minutes.

Intramuscular Administration
NOTE: Although ampicillin; sulbactam may be given IM; the safety and efficacy of IM administration have not been established in pediatric patients.
-Vials: reconstitute 1.5 or 3 g vial with 3.2 or 6.4 mL, respectively, of sterile water for injection or 0.5% or 2% lidocaine HCl to give a solution containing 375 mg/mL ampicillin; sulbactam (250 mg of ampicillin and 125 mg of sulbactam per mL).
-Use only freshly prepared solutions and administer within 1 hour after preparing.
-Inject deeply into a large muscle mass (e.g., anterolateral thigh for infants less than 1 year of age; the deltoid muscle of the upper arm in older children and adolescents).

Most of the adverse events data reflect the incidence in adult clinical trials. However, pediatric safety data demonstrates a similar adverse events profile to that observed in adult patients.

Gastrointestinal adverse events are some of the most common adverse events reported during ampicillin; sulbactam therapy in children. In a clinical study of 234 children, diarrhea (1.9%) and vomiting (1.3%) were reported in ampicillin; sulbactam patients. Nausea, flatulence, abdominal distention, glossitis, and mucosal bleeding have been reported in less than 1% of adult patients. Gastrointestinal adverse reactions that have been reported with postmarketing use of ampicillin; sulbactam or ampicillin include abdominal pain, melena, gastritis, stomatitis, dyspepsia, and black "hairy" tongue (tongue discoloration).

Microbial overgrowth and superinfection can occur with antibiotic use. Candidiasis (less than 1%) may occur as oral candidiasis (rare) or vaginal candidiasis. C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis has been reported with ampicillin; sulbactam. 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.

Serious and sometimes fatal hypersensitivity reactions, including anaphylactoid reactions and anaphylactic shock, have been reported during therapy with penicillins, including ampicillin; sulbactam. Other dermatologic or hypersensitivity-related reactions include rash (less than 2%), itching/pruritus (less than 1%), erythema (less than 1%), and tightness in the throat (less than 1%). Reactions that have been reported with postmarketing use of ampicillin; sulbactam or ampicillin include angioedema, erythema multiforme, exfoliative dermatitis, dermatitis, urticaria, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The incidence of rash secondary to ampicillin seems to be higher in patients with viral illnesses, such as mononucleosis. Acute myocardial ischemia, with or without myocardial infarction, may occur as part of an allergic reaction.

Headache was reported in less than 1% of ampicillin; sulbactam adult patients in trials. Other nervous system adverse reactions reported with postmarketing use of ampicillin; sulbactam or ampicillin include seizures (convulsions) and dizziness. Convulsions have been associated with high cerebrospinal fluid concentrations of beta-lactams.

Hematologic effects reported with ampicillin; sulbactam include decreased platelets, decreased neutrophils, decreased hemoglobin, decreased hematocrits, decreased red blood cells, decreased white blood cells, decreased lymphocytes, increased lymphocytes, increased monocytes, increased basophils, increased eosinophils, and increased platelets. Atypical lymphocytosis has been reported rarely in pediatric patients receiving ampicillin; sulbactam. During postmarketing use of the ampicillin; sulbactam or ampicillin, cases of agranulocytosis, hemolytic anemia, and thrombocytopenic purpura have been reported. In a clinical study of 234 children, abnormal neutrophil and eosinophil counts were some of the most common laboratory abnormalities reported in patients who received ampicillin; sulbactam. Hematologic adverse events are usually reversible upon discontinuation of therapy and may be associated with hypersensitivity. 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.

Injection site reaction has been reported with the use of ampicillin; sulbactam. In clinical trials in adult patients, local adverse reactions included pain at the IM injection site (16%), pain at the IV injection site (3%), and thrombophlebitis/phlebitis (1.2% to 3%). Similar local reactions may be seen in pediatric patients as well.

General adverse reactions reported in less than 1% of adult patients during ampicillin; sulbactam therapy include fatigue, malaise, chest pain (unspecified), edema, chills, substernal pain, and epistaxis.

Urinary or renal adverse events reported in less than 1% of adult patients during ampicillin; sulbactam therapy include urinary retention and dysuria. Azotemia (increased BUN) and increased serum creatinine have also occurred. The presence of red blood cells and hyaline casts in the urinalysis has also been noted. Cases of tubulo-interstitial nephritis have been reported during postmarketing use of ampicillin; sulbactam or ampicillin.

Elevated hepatic enzymes, including AST (SGOT), ALT (SGPT), alkaline phosphatase, and LDH, have been reported in patients during ampicillin; sulbactam therapy. In a clinical study of 234 children, abnormal aspartate aminotransferase (AST) was one of the most common laboratory abnormalities reported in patients who received ampicillin; sulbactam. Cases of cholestatic hepatitis, cholestasis, hyperbilirubinemia, jaundice, and hepatic dysfunction have been reported during postmarketing use of ampicillin; sulbactam or ampicillin.

Decreased serum albumin (hypoalbuminemia) and total proteins have been reported in patients receiving ampicillin; sulbactam therapy.

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 to 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.

Dyspnea has been reported during postmarketing use of ampicillin; sulbactam.

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

Use ampicillin; sulbactam with caution in patients with renal impairment since both drug components are eliminated renally. The dosage interval should be adjusted in those patients with CrCl <= 50 mL/minute and in those patients with renal failure, including patients receiving dialysis. During prolonged therapy in patients without preexisting renal impairment, renal function should be periodically evaluated.

Penicillin antibiotics, such as ampicillin; sulbactam, have been associated with a variety of hypersensitivity reactions ranging from mild rash to fatal anaphylaxis. Prior to initiating treatment, all patients should be questioned about previous hypersensitivity reactions. If a mild to moderate reaction has been identified, the drug may be administered with caution; however, for those patients who have previously experienced a severe (e.g., anaphylaxis or Stevens-Johnson syndrome) penicillin hypersensitivity, cephalosporin hypersensitivity, and/or carbapenem hypersensitivity reaction, use of ampicillin; sulbactam is contraindicated. Other patients who are at increased risk for hypersensitivity reactions include patients with allergies or allergic conditions such as asthma, eczema, hives (urticaria), or hay fever. If an allergic reaction develops during use of ampicillin; sulbactam, discontinue treatment and institute appropriate therapy.

Ampicillin; sulbactam is contraindicated for use in patients with a history of cholestasis with jaundice or other hepatic dysfunction caused by ampicillin; sulbactam. Hepatotoxicity, including cholestatic jaundice and hepatitis, has been associated with ampicillin; sulbactam. Use ampicillin; sulbactam with caution in patients with hepatic disease, and monitor liver function at regular intervals during therapy in these patients. Although hepatic dysfunction due to ampicillin; sulbactam is usually reversible, deaths have been reported.

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

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; sulbactam, 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.

Serious rash events, such as toxic epidermal necrolysis, Stevens-Johnson syndrome, exfoliative dermatitis, and acute generalized exanthematous pustulosis (AGEP), have been reported in patients receiving treatment with ampicillin; sulbactam. If a severe skin reaction occurs, discontinue ampicillin; sulbactam and institute appropriate therapy.

Description: Ampicillin; sulbactam is a parenteral antibiotic that combines ampicillin with sulbactam, a beta-lactamase inhibitor, in a 2:1 ratio. The antimicrobial coverage of ampicillin; sulbactam is similar to the oral agent amoxicillin; clavulanic acid. Sulbactam alone has weak antibacterial activity. In combination with sulbactam, ampicillin's spectrum is broadened to include many beta-lactamase-producing organisms. Ampicillin; sulbactam is used mainly in children to treat infections such as moderate to severe intra-abdominal infections and skin and soft-tissue infections caused by susceptible organisms. It is also used for lower respiratory tract infections, urinary tract infections, endocarditis, and for the treatment of severe sinusitis. Ampicillin; sulbactam is not indicated for meningitis. The dosage of ampicillin; sulbactam should be based on the ampicillin component; however, confirmation that the dose was written on the ampicillin component and not ampicillin; sulbactam should occur. Ampicillin; sulbactam is FDA-approved for skin and skin structure infections in pediatric patients as young as 1 year of age.

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: Acinetobacter calcoaceticus, Bacteroides fragilis, Bacteroides sp., Clostridium sp., Enterococcus faecalis, Escherichia coli, Haemophilus influenzae (beta-lactamase negative), Haemophilus influenzae (beta-lactamase positive), Klebsiella pneumoniae, Klebsiella sp., Moraxella catarrhalis, Morganella morganii, Neisseria gonorrhoeae, Peptococcus sp., Peptostreptococcus sp., Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Staphylococcus aureus (MSSA), Staphylococcus epidermidis, Staphylococcus saprophyticus, Streptococcus pneumoniae, Streptococcus pyogenes (group A beta-hemolytic streptococci), 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.

For the treatment of community-acquired pneumonia (CAP)* and pleural empyema*:
-for the treatment of community-acquired pneumonia (CAP)*:
Intravenous dosage:
Premature neonates: 100 mg/kg/day ampicillin component (150 mg/kg/day ampicillin; sulbactam) IV divided every 12 hours has been suggested based on very limited pharmacokinetic data (n = 15) in premature neonates given ampicillin and sulbactam in a 1:1 ratio.
Neonates: 100 mg/kg/day ampicillin component (150 mg/kg/day ampicillin; sulbactam) IV divided every 8 hours based on limited data in neonates for other indications.
Infants, Children, and Adolescents: 100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours (Max: 8 g/day ampicillin [12 g/day ampicillin; sulbactam]) for 5 to 7 days. Doses up to 400 mg/kg/day ampicillin component (600 mg/kg/day ampicillin; sulbactam) have rarely been reported for serious infections. In persons living with HIV, ampicillin; sulbactam is recommended as part of combination therapy for hospitalized patients.
-for the treatment of community-acquired pleural empyema*:
Intravenous dosage:
Infants, Children, and Adolescents: 100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours (Max: 8 g/day ampicillin [12 g/day ampicillin; sulbactam]). Treat for at least 2 weeks after drainage and defervescence.

For the treatment of skin and skin structure infections, including cellulitis and pyomyositis:
-for the treatment of unspecified skin and skin structure infections:
Intravenous dosage:
Premature Neonates*: 100 mg/kg/day ampicillin component (150 mg/kg/day ampicillin; sulbactam) IV divided every 12 hours has been suggested based on very limited pharmacokinetic data (n = 15) in premature neonates given ampicillin and sulbactam in a 1:1 ratio.
Neonates*: 100 mg/kg/day ampicillin component (150 mg/kg/day ampicillin; sulbactam) IV divided every 8 hours based on limited data in neonates for other indications.
Infants*: 100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours. Doses as high as 400 mg/kg/day ampicillin component (600 mg/kg/day ampicillin; sulbactam) have been reported for serious infections.
Children and Adolescents weighing less than 40 kg: 100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours (Max: 8 g/day ampicillin [12 g/day ampicillin; sulbactam]). Doses as high as 400 mg/kg/day ampicillin component (600 mg/kg/day ampicillin; sulbactam) have been reported for serious infections. The FDA-approved dosage is 200 mg/kg/day ampicillin component (300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours.
Children and Adolescents weighing 40 kg or more: 1.5 g (1 g ampicillin and 0.5 g sulbactam) or 3 g (2 g ampicillin and 1 g sulbactam) IV every 6 hours.
-for the treatment of cellulitis:
Intravenous dosage:
Neonates*: 100 mg/kg/day ampicillin component (150 mg/kg/day ampicillin; sulbactam) IV divided every 8 hours for 5 to 14 days based on limited data in neonates for other indications.
Infants*: 100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours for 5 to 14 days. [66745 Doses as high as 400 mg/kg/day ampicillin component (600 mg/kg/day ampicillin; sulbactam) have been reported for serious infections.
Children and Adolescents weighing less than 40 kg: 100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours (Max: 8 g/day ampicillin [12 g/day ampicillin; sulbactam]) for 5 to 14 days. Doses as high as 400 mg/kg/day ampicillin component (600 mg/kg/day ampicillin; sulbactam) have been reported for serious infections. The FDA-approved dosage is 200 mg/kg/day ampicillin component (300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours.
Children and Adolescents weighing 40 kg or more: 1.5 g (1 g ampicillin and 0.5 g sulbactam) or 3 g (2 g ampicillin and 1 g sulbactam) IV every 6 hours for 5 to 14 days.
-for the treatment of pyomyositis:
Intravenous dosage:
Infants*: 100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours for 14 to 21 days plus vancomycin in patients with underlying conditions. Doses as high as 400 mg/kg/day ampicillin component (600 mg/kg/day ampicillin; sulbactam) have been reported for serious infections.
Children and Adolescents weighing less than 40 kg: 100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours (Max: 8 g/day ampicillin [12 g/day ampicillin; sulbactam]) for 14 to 21 days plus vancomycin in patients with underlying conditions. Doses as high as 400 mg/kg/day ampicillin component (600 mg/kg/day ampicillin; sulbactam) have been reported for serious infections. The FDA-approved dosage is 200 mg/kg/day ampicillin component (300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours.
Children and Adolescents weighing 40 kg or more: 1.5 g (1 g ampicillin and 0.5 g sulbactam) or 3 g (2 g ampicillin and 1 g sulbactam) IV every 6 hours for 14 to 21 days plus vancomycin in patients with underlying conditions.

For the treatment of epiglottitis*:
Intravenous dosage:
Infants, Children, and Adolescents: 100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) (Max: 8 g/day ampicillin [12 g/day ampicillin; sulbactam]) IV divided every 6 hours for 5 to 10 days.

For the treatment of infective endocarditis*:
Intravenous dosage:
Infants: 100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours.
Children and Adolescents: 133 to 200 mg/kg/day ampicillin component (200 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 4 to 6 hours (Max: 8 g/day ampicillin [12 g/day ampicillin; sulbactam]). Guidelines recommend ampicillin; sulbactam plus gentamicin with or without vancomycin for culture-negative, community-acquired native valve endocarditis (NVE) or late (more than 1 year after surgery) prosthetic valve endocarditis (PVE); treat for 4 to 6 weeks for NVE and for 6 weeks with rifampin for PVE. Ampicillin; sulbactam for 4 weeks is recommended for endocarditis due to HACEK microorganisms.

For the treatment of acute bacterial sinusitis* in patients with severe infection requiring hospitalization:
Intravenous dosage:
Infants, Children, and Adolescents: 200 to 400 mg/kg/day ampicillin component (300 to 600 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours (Max: 8 g/day ampicillin [12 g/day ampicillin; sulbactam]) for 10 to 14 days.

For the treatment of suppurative sialadenitis* or parotitis*:
Intravenous dosage:
Neonates: 100 mg/kg/day ampicillin component (150 mg/kg/day ampicillin; sulbactam; frequency not specified) IV for 9 days was successfully used in a case report of a 17-day-old neonate with submandibular sialadenitis. Limited data in neonates suggest dividing the daily dose and administering every 8 hours.
Infants, Children, and Adolescents: 100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours (Max: 8 g/day ampicillin [12 g/day ampicillin; sulbactam]). Doses as high as 400 mg/kg/day ampicillin component (600 mg/kg/day ampicillin; sulbactam) have been reported for serious infections.

For surgical infection prophylaxis*:
Intravenous dosage:
Infants, Children, and Adolescents: 50 mg/kg/dose ampicillin component (75 mg/kg/dose ampicillin; sulbactam) IV as a single dose (Max: 2 g ampicillin component [3 g ampicillin; sulbactam] per dose) within 60 minutes prior to the surgical incision. Intraoperative redosing 2 hours from the first preoperative dose and duration of prophylaxis less than 24 hours for most procedures are suggested by clinical practice guidelines. A longer prophylaxis duration of 48 hours for certain cardiothoracic procedures is controversial. Clinical practice guidelines recommend ampicillin; sulbactam for certain thoracic, biliary tract, colorectal, head and neck, urogynecology, and plastic surgery procedures.

For the treatment of gynecologic infections*, including pelvic inflammatory disease (PID)* and tubo-ovarian abscess*:
-for the general treatment of gynecologic infections*:
Intravenous dosage:
Adolescents: 100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours (Max: 8 g/day ampicillin [12 g/day ampicillin; sulbactam]).
-for the treatment of pelvic inflammatory disease (PID)* and tubo-ovarian abscess*:
Intravenous dosage:
Adolescents: 3 g (2 g ampicillin and 1 g sulbactam) IV every 6 hours in combination with doxycycline as an alternative. Ampicillin; sulbactam should be continued for at least 24 to 48 hours after clinical improvement, and then stepdown to oral doxycycline and metronidazole for a total of 14 days of therapy.

For the treatment of complicated intraabdominal infections* with adequate source control, including peritonitis*, appendicitis*, intraabdominal abscess*:
Intravenous dosage:
Premature Neonates: 100 mg/kg/day ampicillin component (150 mg/kg/day ampicillin; sulbactam) IV divided every 12 hours for 7 to 10 days has been suggested based on very limited pharmacokinetic data (n = 15) in premature neonates given ampicillin and sulbactam in a 1:1 ratio.
Neonates: 100 mg/kg/day ampicillin component (150 mg/kg/day ampicillin; sulbactam) IV divided every 8 hours for 7 to 10 days based on limited data in neonates for other indications.
Infants, Children, and Adolescents: 100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours (Max: 8 g/day ampicillin [12 g/day ampicillin; sulbactam]) for 3 to 7 days. Doses as high as 400 mg/kg/day ampicillin component (600 mg/kg/day ampicillin; sulbactam) have been reported for serious infections.

For the treatment of bone and joint infections*, including osteomyelitis* and infectious arthritis*:
-for the treatment of osteomyelitis*:
Intravenous dosage:
Premature Neonates: 100 mg/kg/day ampicillin component (150 mg/kg/day ampicillin; sulbactam) IV divided every 12 hours has been suggested based on very limited pharmacokinetic data (n = 15) in premature neonates given ampicillin and sulbactam in a 1:1 ratio. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates: 100 mg/kg/day ampicillin component (150 mg/kg/day ampicillin; sulbactam) IV divided every 8 hours based on limited data in neonates for other indications. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants 1 to 2 months: 100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours. Doses as high as 400 mg/kg/day ampicillin component (600 mg/kg/day ampicillin; sulbactam) have been reported for serious infections. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants, Children, and Adolescents 3 months to 17 years: 100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours (Max: 8 g/day ampicillin [12 g/day ampicillin; sulbactam]). Doses as high as 400 mg/kg/day ampicillin component (600 mg/kg/day ampicillin; sulbactam) have been reported for serious infections. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 3 to 4 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.
-for the treatment of infectious arthritis:
Intravenous dosage:
Premature Neonates: 100 mg/kg/day ampicillin component (150 mg/kg/day ampicillin; sulbactam) IV divided every 12 hours has been suggested based on very limited pharmacokinetic data (n = 15) in premature neonates given ampicillin and sulbactam in a 1:1 ratio. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates: 100 mg/kg/day ampicillin component (150 mg/kg/day ampicillin; sulbactam) IV divided every 8 hours based on limited data in neonates for other indications. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants 1 to 2 months: 100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours. Doses as high as 400 mg/kg/day ampicillin component (600 mg/kg/day ampicillin; sulbactam) have been reported for serious infections. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants, Children, and Adolescents 3 months to 17 years: 100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours (Max: 8 g/day ampicillin [12 g/day ampicillin; sulbactam]). Doses as high as 400 mg/kg/day ampicillin component (600 mg/kg/day ampicillin; sulbactam) have been reported for serious infections. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 2 to 3 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.

For the treatment of bacteremia* and sepsis*:
Intravenous dosage:
Premature Neonates: 100 mg/kg/day ampicillin component (150 mg/kg/day ampicillin; sulbactam) IV divided every 12 hours has been suggested based on very limited pharmacokinetic data (n = 15) in premature neonates given ampicillin and sulbactam in a 1:1 ratio.
Neonates: 100 mg/kg/day ampicillin component (150 mg/kg/day ampicillin; sulbactam) IV divided every 8 hours based on limited data in neonates. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.
Infants, Children, and Adolescents: 100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours (Max: 8 g/day ampicillin [12 g/day ampicillin; sulbactam]). Doses as high as 400 mg/kg/day ampicillin component (600 mg/kg/day ampicillin; sulbactam) have been reported for serious infections. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.

For the treatment of anthrax*:
-for the treatment of systemic anthrax* without aerosol exposure, including those with signs and symptoms of meningitis, as part of combination therapy:
Intravenous dosage:
Neonates 32 weeks gestation and older: 50 mg/kg/dose ampicillin component (75 mg/kg/dose ampicillin; sulbactam) IV every 12 hours for at least 14 days; may consider step-down to oral therapy.
Infants, Children, and Adolescents: 50 mg/kg/dose ampicillin component (75 mg/kg/dose ampicillin; sulbactam) (Max: 2 g/dose ampicillin [3 g/day ampicillin; sulbactam]) 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 dosage:
Neonates 32 weeks gestation and older: 50 mg/kg/dose ampicillin component (75 mg/kg/dose ampicillin; sulbactam) IV 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.
Infants, Children, and Adolescents: 50 mg/kg/dose ampicillin component (75 mg/kg/dose ampicillin; sulbactam) (Max: 2 g/dose ampicillin [3 g/day ampicillin; sulbactam]) 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 ampicillin component (75 mg/kg/dose ampicillin; sulbactam) (Max: 2 g/dose ampicillin [3 g/day ampicillin; sulbactam]) 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.

Maximum Dosage Limits:
-Neonates
Safety and efficacy have not been established; however, doses up to 100 mg/kg/day ampicillin component (150 mg/kg/day ampicillin; sulbactam) IV have been used off-label.
-Infants
Safety and efficacy have not been established; however, doses up to 400 mg/kg/day ampicillin component (600 mg/kg/day ampicillin; sulbactam) IV have been used off-label.
-Children
200 mg/kg/day ampicillin component (300 mg/kg/day ampicillin; sulbactam) IV is recommended in the FDA-approved labeling; however, doses up to 400 mg/kg/day ampicillin component (600 mg/kg/day ampicillin; sulbactam) IV have been used off-label (Max: 8 g/day ampicillin [12 g/day ampicillin; sulbactam]).
-Adolescents
200 mg/kg/day ampicillin component (300 mg/kg/day ampicillin; sulbactam) IV is recommended in the FDA-approved labeling; however, doses up to 400 mg/kg/day ampicillin component (600 mg/kg/day ampicillin; sulbactam) IV have been used off-label (Max: 8 g/day ampicillin [12 g/day ampicillin; sulbactam]).

Patients with Hepatic Impairment Dosing
No dosage adjustment is needed.

Patients with Renal Impairment Dosing
The following dosage adjustments are based on a usual dose in pediatric patients of 100 to 200 mg/kg/day ampicillin component (150 to 300 mg/kg/day ampicillin; sulbactam) IV divided every 6 hours :
CrCl 30 to 50 mL/minute/1.73 m2: 35 to 50 mg/kg/dose ampicillin component (52.5 to 75 mg/kg/dose ampicillin; sulbactam) IV every 8 hours.
CrCl 10 to 29 mL/minute/1.73 m2: 35 to 50 mg/kg/dose ampicillin component (52.5 to 75 mg/kg/dose ampicillin; sulbactam) IV every 12 hours.
CrCl less than 10 mL/minute/1.73 m2: 35 to 50 mg/kg/dose ampicillin component (52.5 to 75 mg/kg/dose ampicillin; sulbactam) IV every 24 hours.

Intermittent hemodialysis
35 to 50 mg/kg/dose ampicillin component (52.5 to 75 mg/kg/dose ampicillin; sulbactam) IV every 24 hours.

Peritoneal dialysis
35 to 50 mg/kg/dose ampicillin component (52.5 to 75 mg/kg/dose ampicillin; sulbactam) IV every 24 hours.

Continuous renal replacement therapy (CRRT)
35 to 50 mg/kg/dose ampicillin component (52.5 to 75 mg/kg/dose ampicillin; sulbactam) IV every 8 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. PBPs 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. PBPs 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.

Sulbactam is an irreversible inhibitor of beta-lactamases. Like clavulanic acid, sulbactam inhibits the activity of beta-lactamase Richmond types II, III, IV, V, and VI but not chromosomally mediated type I. Sulbactam has little useful antibacterial activity if used alone. Sulbactam does not alter the actions of ampicillin or the sensitivity of organisms to ampicillin if they are sensitive to ampicillin alone.

The susceptibility interpretive criteria for ampicillin; sulbactam are delineated by pathogen. The MICs are defined for Enterobacterales, Acinetobacter sp., anaerobes, and Vibrio sp. (excluding V. cholerae) as susceptible at 8/4 mcg/mL or less, intermediate at 16/8 mcg/mL, and resistant at 32/16 mcg/mL or more. The MICs are defined for H. influenzae, H. parainfluenzae, Aggregatibacter sp., Cardiobacterium sp., E. corrodens, and Kingella sp. as susceptible at 2/1 mcg/mL or less and resistant at 4/2 mcg/mL or more. The breakpoints for H. influenzae and H. parainfluenzae are based on a dosage regimen of 3 g (2 g ampicillin and 1 g sulbactam) IV every 6 hours. Non-meningitis S. pneumoniae that are susceptible to penicillin are predictably sensitive to ampicillin; sulbactam. Similarly, a Streptococcus sp. beta-hemolytic group organism that is susceptible to penicillin can be considered susceptible to ampicillin; sulbactam. Considering site of infection and appropriate ampicillin; sulbactam dosing, oxacillin-susceptible Staphylococcus sp. can be considered susceptible to ampicillin; sulbactam. The results of ampicillin or penicillin susceptibility tests may be used to predict susceptibility to ampicillin; sulbactam for non-beta-lactamase producing enterococci.

Pharmacokinetics: Ampicillin; sulbactam is administered intravenously or intramuscularly. Protein binding is approximately 28% for ampicillin and 38% for sulbactam. Both drugs are distributed into the lungs, liver, gallbladder, appendix, maxillary sinus, prostate, and other tissues. The drug also distributes very well into various body fluids, such as skin blisters, middle ear effusions, bronchial secretions, urine, and pleural, peritoneal, and synovial fluids. Therapeutic levels are attained within the CSF in the presence of inflammation; however, ampicillin; sulbactam is not indicated for meningitis. The drug and its metabolites are excreted into the urine primarily via tubular secretion and glomerular filtration; approximately 75-85% of both ampicillin and sulbactam are excreted unchanged in the urine after 8 hours. In patients with normal renal function, the elimination half-life of both ampicillin and sulbactam is approximately 1 hour.

Affected cytochrome P450 isoenzymes: none


-Route-Specific Pharmacokinetics
Intravenous Route
The pharmacokinetics in pediatric patients are similar to those observed in adults. In pediatric patients, peak serum and plasma concentrations of 82-446 mcg/ml ampicillin and 44-203 mcg/ml sulbactam were achieved immediately after completion of a 15-minute IV infusion.


-Special Populations
Pediatrics
Neonates
In a pharmacokinetic study in 16 neonates, which included 15 premature neonates (mean gestational age 30 weeks), the mean elimination half-life of ampicillin and sulbactam following a dose of 30 mg/kg or 50 mg/kg (of each drug) was 9.4 +/- 5.95 hours (range, 2-21 hours) and 7.9 +/- 5.58 hours (range, 3-21 hours), respectively. These half-lives were significantly longer than those noted in adult patients (1 hour) reflecting the immature renal function in premature neonates.

Children
The pharmacokinetics of ampicillin; sulbactam are similar in children compared with adults. In a pharmacokinetic study in 28 children (1-12 years) who received ampicillin; sulbactam (40-80 mg/kg/dose every 6 hours), the mean values for clearance, volume of distribution, and elimination half-life for ampicillin were 4.76 ml/min/kg, 0.32 L/kg, and 0.77 hours, respectively. Corresponding values for sulbactam were 4.95 ml/min/kg, 0.34 L/kg, and 0.81 hours, respectively. Pharmacokinetic parameters were not different among age groups.

Hepatic Impairment
Pharmacokinetic data are unavailable in pediatric patients with hepatic impairment. However, ampicillin; sulbactam is not significantly metabolized and pharmacokinetics are not expected to be different in patients with hepatic dysfunction.

Renal Impairment
Pharmacokinetic data are unavailable in pediatric patients with renal impairment. However, ampicillin; sulbactam is primarily excreted renally and clearance has been shown to be significantly prolonged in adult patients with renal impairment. The elimination half-life is prolonged to approximately 5 hours in adults with a CrCl of 15-29 ml/min/1.73 m2 and 9 hours in adults with a CrCl of 5-14 ml/min/1.73 m2. Both ampicillin and sulbactam are removed by hemodialysis.