Note: Ampicillin/sulbactam is a combination product formulated in a 2:1 ratio. Adult dosage recommendations are expressed as total grams of ampicillin/sulbactam.
Usual dosage range: IM, IV: 1.5 to 3 g every 6 hours (maximum: ampicillin/sulbactam 12 g daily) (manufacturer's labeling); for the treatment of infections caused by Acinetobacter spp., higher doses have been described (Assimakopoulos 2019; Beganovic 2021; Betrosian 2008; Gilad 2008; Housman 2013; Levin 2003; Makris 2018; Mosaed 2018).
Bite wound infection, treatment (animal or human bite) (off-label use): IV: 1.5 to 3 g every 6 hours (IDSA [Stevens 2014]); some experts prefer 3 g every 6 hours (Baddour 2021a; Baddour 2021b). Duration of treatment for established infection is typically 5 to 14 days (including oral step-down therapy) (Baddour 2021a; Baddour 2021b; IDSA [Stevens 2014]).
Bloodstream infection (off-label use): For pathogen-directed therapy of susceptible organisms:
IV: 3 g every 6 hours (IDSA [Mermel 2009]; Jellison 2001; Murray 2019); for infections caused by Acinetobacter spp., higher doses (eg, 3 g every 4 hours or 9 g every 8 hours) have been described but comparative data are lacking (Gilad 2008; Housman 2013; Levin 2003). Usual duration is 7 to 14 days; individualize depending on organism, source of infection, and clinical response. A 7-day duration is recommended for patients with uncomplicated Enterobacteriaceae infection who respond appropriately to antibiotic therapy (Kanafani 2019; Moehring 2019; Yahav 2018).
Diabetic foot infection, moderate to severe: IV: 3 g every 6 hours (Harkless 2005). Usual duration of therapy (including oral step-down therapy) is 2 to 4 weeks (in the absence of osteomyelitis) (Harkless 2005; IDSA [Lipsky 2012]; Weintrob 2020).
Endocarditis, treatment (off-label use): Enterococcus (native or prosthetic valve; beta-lactamase–producing strains susceptible to aminoglycosides):
IV: 3 g every 6 hours in combination with gentamicin for 6 weeks (AHA [Baddour 2015]).
Odontogenic infection, pyogenic (off-label use): IV: 3 g every 6 hours; duration is 7 to 14 days (including oral step-down therapy) (Chow 2019).
Pelvic infections (alternative agent):
Intra-amniotic infection (chorioamnionitis): IV: 3 g every 6 hours. Continue until vaginal delivery or for 1 dose after cesarean delivery (ACOG 2017). Note: Some experts recommend 1 additional dose after vaginal delivery and extension of antibiotics after cesarean delivery until patient is afebrile and asymptomatic ≥48 hours (Tita 2019).
Pelvic inflammatory disease (including tubo-ovarian abscess) (alternative agent): IV: 3 g every 6 hours in combination with doxycycline. After 24 to 48 hours of sustained clinical improvement, may transition to oral therapy to complete 14 days of treatment (CDC [Workowski 2021).
Postpartum endometritis: IV: 3 g every 6 hours; treat until patient is clinically improved (no fundal tenderness) and afebrile for 24 to 48 hours (Chen 2021; Gall 1996).
Peritonitis, treatment (peritoneal dialysis patients): Pathogen-directed therapy for susceptible organisms. Note: Intraperitoneal administration is preferred to IV administration. Duration of therapy is ≥2 weeks for patients with adequate clinical response (Burkart 2019; ISPD [Li 2016]). Consider a 25% dose increase in patients with significant residual renal function (urine output >100 mL/day) (ISPD [Li 2010]; ISPD [Li 2016]; Mancini 2018; Szeto 2018).
Intermittent (preferred): Intraperitoneal: 3 g per exchange every 12 hours; allow to dwell for ≥6 hours (Blackwell 1990; ISPD [Li 2016]).
Continuous (with every exchange) (dose is per liter of dialysate): Intraperitoneal: Loading dose: 750 mg/L to 1 g/L of dialysate with first exchange of dialysate; maintenance dose: 100 mg/L of dialysate with each subsequent exchange (ISPD [Li 2016]; Lam 2008).
Pneumonia (off-label use):
Aspiration pneumonia, community-acquired (nonsevere): IV: 1.5 to 3 g every 6 hours, generally for 5 days (including oral step-down therapy) (Klompas 2021).
Community-acquired pneumonia: Inpatients without risk factors for P. aeruginosa: IV: 3 g every 6 hours in combination with other agent(s) when appropriate. Total duration (including oral step-down therapy) is a minimum of 5 days; patients should be clinically stable with normal vital signs prior to discontinuation (ATS/IDSA [Metlay 2019]; Majcher-Peszynska 2014; Rossoff 1995).
Hospital-acquired or ventilator-associated pneumonia: IV: 3 g every 6 hours, as part of a combination regimen when appropriate. Duration of therapy varies based on disease severity and response to therapy; treatment is typically given for 7 days (Chan 2010; IDSA/ATS [Kalil 2016]; Ye 2016; Zalts 2016). Note: For infections caused by Acinetobacter spp., higher doses (eg, 3 g every 4 hours or 9 g every 8 hours) have been described but comparative data are lacking (Assimakopoulos 2019; Beganovic 2021; Betrosian 2008; Gilad 2008; Housman 2013; Levin 2003; Makris 2018; Mosaed 2018).
Surgical prophylaxis (off-label use): IV: 3 g within 60 minutes prior to surgical incision. Doses may be repeated in 2 hours if procedure is lengthy or if there is excessive blood loss. Note: Consider local susceptibility patterns prior to use (Anderson 2019; ASHP/IDSA/SIS/SHEA [Bratzler 2013]). In cases in which extension of prophylaxis is warranted postoperatively, total duration should be ≤24 hours (Anderson 2019). Postoperative prophylaxis is not recommended in clean and clean-contaminated surgeries (CDC [Berríos-Torres 2017]).
Surgical site infections (eg, intestinal, GU tract, abdominal wall) (off-label use): IV: 3 g every 6 hours. Duration depends on extent and severity of infection as well as response to therapy; may switch to oral treatment when clinically improved. Note: Consult local susceptibility patterns prior to empiric use (IDSA [Stevens 2014]; Mancino 2020).
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Note: Renally adjusted dose recommendations are based on a usual recommended dose of 1.5 to 3 g every 6 hours and are expressed as total grams of ampicillin/sulbactam.
Altered kidney function: IV:
Note: Estimation of renal function for the purpose of drug dosing should be done using the Cockcroft-Gault formula. Dosage recommendations are expressed as grams of ampicillin/sulbactam combination (Wright 1983; manufacturer's labeling):
CrCl ≥30 mL/minute: No dosage adjustment necessary.
CrCl 15 to 29 mL/minute: 1.5 to 3 g every 12 hours.
CrCl 5 to 14 mL/minute: 1.5 to 3 g every 24 hours.
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2): Augmented renal clearance (ARC) is a condition that occurs in certain critically-ill patients without organ dysfunction and with normal serum creatinine concentrations. Young patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Bilbao-Meseguer 2018; Udy 2010).
IV: 1.5 to 3 g every 4 to 6 hours (expert opinion).
Hemodialysis, intermittent (thrice weekly): Dialyzable (39% to 63% [Jusko 1973]):
IV: 1.5 to 3 g every 12 to 24 hours; administer after dialysis when scheduled dose falls on dialysis days (Heintz 2009).
Peritoneal dialysis: IV: 1.5 g every 12 hours or 3 g every 24 hours (Blackwell 1990; expert opinion).
CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection) and consideration of initial loading doses. Close monitoring of response and adverse reactions (eg, neurotoxicity) due to drug accumulation is important.
CVVH/CVVHD/CVVHDF: IV: 3 g every 8 to 12 hours (Heintz 2009; expert opinion).
PIRRT (eg, sustained, low-efficiency diafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection) and consideration of initial loading doses. Close monitoring of response and adverse reactions (eg, neurotoxicity) due to drug accumulation is important.
IV: Initial: 3 g followed by 1.5 to 3 g every 8 to 12 hours. Where possible, give one dose after PIRRT session (Lorenzen 2012; expert opinion).
There is no dosage adjustment provided in the manufacturer’s labeling.
(For additional information see "Ampicillin and sulbactam: Pediatric drug information")
Note: Unasyn (ampicillin/sulbactam) is a combination product formulated in a 2:1 ratio (eg, each 3 g vial contains 2 g of ampicillin and 1 g of sulbactam); review dosing units carefully. Dosage recommendations are expressed as either mg of the ampicillin component or as total grams of the ampicillin/sulbactam combination within the dosing field; review dosing units in each indication carefully.
General dosing, susceptible infection: Infants, Children, and Adolescents:
Mild to moderate infection: IV: 100 to 200 mg ampicillin/kg/day divided every 6 hours; maximum dose: 2,000 mg ampicillin/dose (Red Book [AAP 2018]); may also be administered IM (Bradley 2018)
Severe infection (eg, meningitis, resistant Streptococcus pneumonia): IV: 200 to 400 mg ampicillin/kg/day divided every 6 hours; maximum dose: 2,000 mg ampicillin/dose (Bradley 2018; Red Book [AAP 2018]); may also be administered IM (Bradley 2018)
Endocarditis, treatment: Children and Adolescents: IV: 200 to 300 mg ampicillin/kg/day divided every 4 to 6 hours; maximum dose: 2,000 mg ampicillin/dose; may use in combination with gentamicin, vancomycin, and/or rifampin (optional; dependent upon organism) for at least 4 to 6 weeks; some organisms may require longer duration (AHA [Baltimore 2015])
Intra-abdominal infection, complicated: Infants, Children, and Adolescents: IV: 200 mg ampicillin/kg/day divided every 6 hours; Note: Due to high rates of E. coli resistance, not recommended for the treatment of community-acquired intra-abdominal infections (IDSA [Solomkin 2010])
Pelvic inflammatory disease: Adolescents: IV: 3 g ampicillin/sulbactam every 6 hours with doxycycline (CDC [Workowski 2015])
Rhinosinusitis, severe infection requiring hospitalization: Children and Adolescents: IV: 200 to 400 mg ampicillin/kg/day divided every 6 hours for 10 to 14 days; maximum dose: 2,000 mg ampicillin/dose (IDSA [Chow 2012])
Skin and skin structure infection: Children and Adolescents: IV: 200 mg ampicillin/kg/day divided every 6 hours for up to 14 days; maximum dose: 2,000 mg ampicillin/dose
Surgical prophylaxis: Children and Adolescents: IV: 50 mg ampicillin/kg/dose within 60 minutes prior to procedure; may repeat in 2 hours if lengthy procedure or excessive blood loss; maximum dose: 2,000 mg ampicillin/dose (Bratzler 2013)
Children and Adolescents: IV:
CrCl ≥30 mL/minute/1.73 m2: No dosage adjustment required.
CrCl 15 to 29 mL/minute/1.73 m2: Administer every 12 hours.
CrCl 5 to 14 mL/minute/1.73 m2: Administer every 24 hours.
There are no dosage adjustments provided in the manufacturer’s labeling.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution Reconstituted, Injection:
Generic: 3 g: Ampicillin 2 g and sulbactam 1 g (1 ea [DSC])
Solution Reconstituted, Injection [preservative free]:
Unasyn: 3 g: Ampicillin 2 g and sulbactam 1 g (1 ea); 1.5 g: Ampicillin 1 g and sulbactam 0.5 g (1 ea)
Generic: 1.5 g: Ampicillin 1 g and sulbactam 0.5 g (1 ea); 3 g: Ampicillin 2 g and sulbactam 1 g (1 ea)
Solution Reconstituted, Intravenous [preservative free]:
Unasyn: 15 g: Ampicillin 10 g and sulbactam 5 g (1 ea)
Generic: 1.5 g: Ampicillin 1 g and sulbactam 0.5 g (1 ea); 15 g: Ampicillin 10 g and sulbactam 5 g (1 ea); 3 g: Ampicillin 2 g and sulbactam 1 g (1 ea)
Yes
Administer around-the-clock to promote less variation in peak and trough serum levels.
IV: Administer by slow injection over 10 to 15 minutes or as an IV infusion over 15 to 30 minutes. Ampicillin and gentamicin should not be mixed in the same IV tubing.
Some penicillins (eg, ampicillin, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate aminoglycosides in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent Y-site administration should be avoided.
IM: Inject deep IM into large muscle mass; a concentration of 375 mg/mL ampicillin/sulbactam (250 mg ampicillin/125 mg sulbactam per mL) is recommended; may be diluted in sterile water or lidocaine 0.5% or lidocaine 2% for IM administration.
Parenteral:
IM: Administer by deep IM injection. Administer within 1 hour of preparation.
IV: Administered by slow IV injection over 10 to 15 minutes or by intermittent IV infusion over 15 to 30 minutes
Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate aminoglycosides in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concomitant use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment; however, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside concentrations, CBC, and clinical response should be considered.
Bacterial infections: Treatment of skin and skin structure, intra-abdominal, and gynecological infections caused by susceptible bacteria; spectrum is that of ampicillin plus organisms producing beta-lactamases such as Staphylococcus aureus, Haemophilus influenzae, Escherichia coli, Klebsiella, Acinetobacter, Enterobacter, and anaerobes.
Bite wound infection, treatment (animal or human bite); Bloodstream infection; Endocarditis, treatment; Odontogenic infection, pyogenic; Pneumonia; Surgical prophylaxis; Surgical site infections (eg, intestinal, GU tract, abdominal wall)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Also see Ampicillin.
>10%: Local: Pain at injection site (IM: 16%; IV: 3%)
1% to 10%:
Cardiovascular: Phlebitis (1%), thrombophlebitis (3%)
Dermatologic: Skin rash (<2%)
Gastrointestinal: Diarrhea (3%)
<1%:
Cardiovascular: Chest pain, edema, substernal pain
Dermatologic: Erythema of skin, facial swelling, pruritus
Gastrointestinal: Abdominal distention, flatulence, glossitis, nausea, vomiting
Genitourinary: Dysuria, urinary retention
Hematologic & oncologic: Lymphocytosis (atypical), mucous membrane bleeding
Infection: Candidiasis
Nervous system: Chills, fatigue, headache, malaise
Respiratory: Constriction of the pharynx, epistaxis
Frequency not defined:
Endocrine & metabolic: Decreased serum albumin, decreased serum total protein, increased lactate dehydrogenase
Genitourinary: Casts in urine (hyaline), finding of blood in urine
Hematologic: Basophilia, decreased hematocrit, decreased hemoglobin, decreased neutrophils, decreased red blood cells, eosinophilia, leukopenia, lymphocytopenia, monocytosis, thrombocythemia, thrombocytopenia
Hepatic: Increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate aminotransferase
Renal: Increased blood urea nitrogen, increased serum creatinine
Postmarketing:
Dermatologic: Acute generalized exanthematous pustulosis, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria
Gastrointestinal: Abdominal pain, cholestasis, Clostridioides difficile associated diarrhea, dyspepsia, gastritis, hairy tongue, melena, stomatitis
Hematologic & oncologic: Agranulocytosis, hemolytic anemia, immune thrombocytopenia, positive direct Coombs test
Hepatic: Cholestatic hepatitis, cholestatic jaundice, hepatitis, hyperbilirubinemia, jaundice
Hypersensitivity: Anaphylaxis, angioedema, hypersensitivity reaction
Local: Injection site reaction
Nervous system: Dizziness, seizure
Renal: Interstitial nephritis
Respiratory: Dyspnea
Hypersensitivity (eg, anaphylaxis or Stevens-Johnson syndrome) to ampicillin, sulbactam, or to other beta-lactam antibacterial drugs (eg, penicillins, cephalosporins), or any component of the formulations; history of cholestatic jaundice or hepatic dysfunction associated with ampicillin/sulbactam
Concerns related to adverse effects:
• Anaphylactoid/hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity or a history of sensitivity to multiple allergens. Patients with a history of penicillin hypersensitivity have experienced severe reactions when treated with cephalosporins. Before initiating therapy, carefully investigate previous penicillin, cephalosporin, or other allergen hypersensitivity. If an allergic reaction occurs, discontinue and institute appropriate therapy.
• Hepatic dysfunction: Hepatitis and cholestatic jaundice have been reported (including fatalities). Toxicity is usually reversible. Monitor hepatic function at regular intervals in patients with hepatic impairment.
• Rash: Appearance of a rash should be carefully evaluated to differentiate a nonallergic ampicillin rash from a hypersensitivity reaction; rash occurs in 5% to 10% of children and is a generalized dull red, maculopapular rash, generally appearing 3-14 days after the start of therapy. It normally begins on the trunk and spreads over most of the body. It may be most intense at pressure areas, elbows, and knees.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• Hepatic impairment: Hepatotoxicity has been reported. Monitor hepatic function at regular intervals in patients with hepatic impairment.
• Infectious mononucleosis: A high percentage of patients with infectious mononucleosis have developed rash during therapy; ampicillin-class antibacterials are not recommended in these patients.
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended.
None known.
Acemetacin: May increase the serum concentration of Penicillins. Risk C: Monitor therapy
Allopurinol: May enhance the potential for allergic or hypersensitivity reactions to Ampicillin. Risk C: Monitor therapy
Aminoglycosides: Penicillins may decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Risk C: Monitor therapy
Atenolol: Ampicillin may decrease the bioavailability of Atenolol. Risk C: Monitor therapy
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Chloroquine: May decrease the serum concentration of Ampicillin. Management: Separate the administration of ampicillin and chloroquine by at least 2 hours to minimize any potential negative impact of chloroquine on ampicillin bioavailability. Risk D: Consider therapy modification
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination
Dichlorphenamide: Penicillins may enhance the hypokalemic effect of Dichlorphenamide. Risk C: Monitor therapy
Immune Checkpoint Inhibitors: Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors. Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Lanthanum: May decrease the serum concentration of Ampicillin. Management: Administer oral ampicillin at least two hours before or after lanthanum. Risk D: Consider therapy modification
Methotrexate: Penicillins may increase the serum concentration of Methotrexate. Risk C: Monitor therapy
Mycophenolate: Penicillins may decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Penicillins. Risk C: Monitor therapy
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification
Tetracyclines: May diminish the therapeutic effect of Penicillins. Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Penicillins may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Both ampicillin and sulbactam cross the placenta (Foulds 1986; Maberry 1992).
Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of ampicillin/sulbactam may be altered (Chamberlain 1993; Foulds 1986).
As a class, penicillin antibiotics are widely used in pregnant patients. Based on available data, penicillin antibiotics are generally considered compatible for use during pregnancy (Ailes 2016; Bookstaver 2015; Crider 2009; Damkier 2019; Lamont 2014; Muanda 2017a; Muanda 2017b).
Untreated intra-amniotic infection (chorioamnionitis) may lead to adverse pregnancy outcomes (including pneumonia, meningitis, and sepsis) in the newborn. Maternal complications may include postpartum uterine atony with hemorrhage, endometritis, peritonitis, sepsis, or adult respiratory distress syndrome. Ampicillin/sulbactam is an alternative option for the treatment of intra-amniotic infection (ACOG 2017).
Antibiotic prophylaxis is recommended prior to all cesarean deliveries unless the patient is already receiving an appropriate antibiotic. A single dose of a targeted antibiotic administered within 60 minutes prior to the delivery is recommended; ampicillin/sulbactam has been evaluated for this purpose, although other antibiotics may be preferred (consult current recommendations) (ACOG 2018).
Ampicillin and sulbactam are present in breast milk.
A review article notes the exposure of ampicillin and sulbactam to a breastfeeding infant would be ~1% to 2% of a typical adult dose (Foulds 1986).
The manufacturer recommends that caution be used if administering to breastfeeding patients. Ampicillin is considered compatible with breastfeeding when used in usual recommended doses. In general, antibiotics that are present in breast milk may cause nondose-related modification of bowel flora. Monitor infants for GI disturbances (WHO 2002).
Also refer to the Ampicillin monograph.
Some products may contain sodium.
With prolonged therapy, monitor hematologic, renal, and hepatic function; monitor for signs of anaphylaxis during first dose. In patients with preexisting hepatic impairment, monitor hepatic function at regular intervals.
Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested. The addition of sulbactam, a beta-lactamase inhibitor, to ampicillin extends the spectrum of ampicillin to include some beta-lactamase-producing organisms.
Ampicillin: See Ampicillin monograph.
Sulbactam:
Distribution: Widely distributed to bile, blister, and tissue fluids; poor penetration into CSF with uninflamed meninges; higher concentrations attained with inflamed meninges; Vd (Nahata 1999):
Children 1 to 12 years: ~0.35 L/kg
Adults: 0.25 L/kg
Protein binding: 38%
Half-life elimination: Children 1 to 12 years (normal renal function): Mean range: ~0.7 to 0.9 hours (Nahata 1999); Adults (normal renal function): 1 to 1.3 hours; Note: Elimination kinetics of both ampicillin and sulbactam are similarly affected in patients with renal impairment, therefore, the blood concentration ratio is expected to remain constant regardless of renal function.
Excretion: Urine (~75% to 85% as unchanged drug) within 8 hours
Anti-infective considerations:
Parameters associated with efficacy:
Ampicillin: See Ampicillin monograph.
Sulbactam (in combination with ampicillin):
Time dependent; associated with time free drug concentration (fT) > minimum inhibitory concentration (MIC):
Acinetobacter baumannii: Goal: ≥40% to 60% fT > MIC (bactericidal) (Yokoyama 2014; Yokoyama 2015).
Expected drug exposure in patients with normal renal function:
Children <12 years of age: Cmax (peak): IV:
15- to 40-minute infusion, steady state: 40 to 80 mg/kg/dose every 6 hours: Ampicillin: 177 to 200 mg/L; sulbactam 81.9 to 102 mg/L (Nahata 1999).
Adults: Cmax (peak):
Note: Adult doses are expressed as the combined amount of ampicillin and sulbactam.
IV: 15-minute infusion, single dose:
1.5 g: Ampicillin: 40 to 71 mg/L; sulbactam: 21 to 40 mg/L.
3 g: Ampicillin: 109 to 150 mg/L; sulbactam: 48 to 88 mg/L.
IM:
1.5 g: Ampicillin: 8 to 37 mg/L; sulbactam: 6 to 24 mg/L.
Solution (reconstituted) (Ampicillin-Sulbactam Sodium Injection)
1.5 (1-0.5) g (per each): $3.25 - $9.54
3 (2-1) g (per each): $5.51 - $19.14
Solution (reconstituted) (Ampicillin-Sulbactam Sodium Intravenous)
1.5 (1-0.5) g (per each): $6.46
3 (2-1) g (per each): $11.08 - $11.09
15 (10-5) g (per each): $47.52 - $90.00
Solution (reconstituted) (Unasyn Injection)
1.5 (1-0.5) g (per each): $9.25
3 (2-1) g (per each): $17.47
Solution (reconstituted) (Unasyn Intravenous)
15 (10-5) g (per each): $87.37
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