Ampicillin and Sulbactam
(am pi SIL in & SUL bak tam)
- Ampicillin Sodium/Sulbactam Na
- Sulbactam and Ampicillin
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution: 1.5 g: Ampicillin 1 g and sulbactam 0.5 g; 3 g: Ampicillin 2 g and sulbactam 1 g; 15 g: Ampicillin 10 g and sulbactam 5 g
1.5 g: Ampicillin 1 g and sulbactam 0.5 g [contains sodium 115 mg (5 mEq)/1.5 g)]
3 g: Ampicillin 2 g and sulbactam 1 g [contains sodium 115 mg (5 mEq)/1.5 g)]
15 g: Ampicillin 10 g and sulbactam 5 g [bulk package; contains sodium 115 mg (5 mEq)/1.5 g)]
Brand Names: U.S.
- Antibiotic, Penicillin
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.
Sulbactam: 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
Sulbactam: Urine (~75% to 85% as unchanged drug) within 8 hours
Sulbactam: 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.
Use: Labeled Indications
Bacterial infections: Treatment of susceptible bacterial infections involved with skin and skin structure, intra-abdominal infections, gynecological infections; spectrum is that of ampicillin plus organisms producing beta-lactamases such as S. aureus, H. influenzae, E. coli, Klebsiella, Acinetobacter, Enterobacter, and anaerobes
Off Label Uses
Acute bacterial rhinosinusitis
Based on the Infectious Diseases Society of America (IDSA) guidelines for acute bacterial rhinosinusitis (ABRS) in children and adults, ampicillin/sulbactam is effective and recommended for the treatment of severe ABRS requiring hospitalization.
Bite wounds (animal/human)
Based on the Infectious Diseases Society of America (IDSA) guidelines for the diagnosis and management of skin and soft tissue infections (SSTI), ampicillin/sulbactam is an effective and recommended treatment of bite wounds.
Endocarditis, treatment (adults)
Based on the American Heart Association (AHA) Scientific Statement for Infective Endocarditis in Adults, ampicillin and sulbactam in combination with an aminoglycoside is an effective and recommended treatment option for infective endocarditis (native or prosthetic valve) due to beta-lactamase-producing strains of Enterococcus that are penicillin resistant/aminoglycoside- and vancomycin-susceptible.
Endocarditis, treatment (pediatric)
Based on the AHA Scientific Statement for Infective Endocarditis in Childhood, ampicillin and sulbactam, is an effective and recommended agent for endocarditis, depending on organism. May be used as monotherapy or in combination with other antibiotics, depending on organism.
Complicated intra-abdominal infections in pediatric patients [Solomkin 2010].
Intravascular catheter-associated bloodstream infection
Based on the Infectious Diseases Society of America (IDSA) guidelines for the diagnosis and management of intravascular catheter-related infection, ampicillin/sulbactam is an effective and recommended treatment of infection with susceptible organisms (eg, Acinetobacter spp).
Pneumonia, community acquired
Data from a multicenter, prospective, noncomparative, open-label clinical pharmacokinetic study in patients with community acquired pneumonia supports the use of ampicillin/sulbactam at an interval of every 6 hours rather than an every 8 hour or longer interval (sometimes described in other community-acquired pneumonia [CAP] studies) based on pharmacokinetic analyses in vivo [Majcher-Peszynska 2014]. An older randomized, prospective, parallel-group, comparative study, in patients with lower respiratory tract infections did not specify the diagnosis of CAP; however, the pathogens collected for many of the patients likely confirmed CAP [Geckler 1994]. Of note, the definition of clinical cure, improvement, and failure in this study were subjective. Additional data may be necessary to further define the role of ampicillin/sulbactam in this condition.
Pneumonia, hospital acquired or ventilator-associated due to Acinetobacter
Based on the IDSA and ATS Guidelines for the Management of Adults with Hospital-acquired and Ventilator-associated Pneumonia, ampicillin and sulbactam is effective and recommended for the treatment of hospital-acquired (HAP) or ventilator-associated pneumonia (VAP) caused by susceptible Acinetobacter species.
Based on the American Society of Health-System Pharmacists (ASHP), the Infectious Diseases Society of America (IDSA), the Surgical Infection Society (SIS), and the Society for Healthcare Epidemiology of America (SHEA) guidelines for antimicrobial prophylaxis in surgery, ampicillin and sulbactam is an effective and recommended agent for prophylaxis of surgical procedures (eg, certain thoracic procedures, biliary tract open or high-risk laparoscopic procedures, colorectal procedures, certain head and neck procedures, hysterectomy, certain urologic procedures, and plastic surgery).
Surgical site infections
Based on the Infectious Diseases Society of America (IDSA) guidelines for the diagnosis and management of skin and soft tissue infections (SSTI), ampicillin/sulbactam, in combination with gentamicin or tobramycin, is an effective and recommended option for treatment of surgical site infections occurring after surgery of the intestinal or genitourinary tract. Systemic antibacterials are not routinely indicated for surgical site infections, but may be beneficial (in conjunction with suture removal plus incision and drainage) in patients with significant systemic response (eg, temperature >38.5ºC, heart rate >110 beats per minute, erythema/induration extending >5 cm from incision, WBC >12,000/mm3).
Additional Off-Label Uses
Complicated intra-abdominal infections in pediatric patients (IDSA [Solomkin 2010])
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
Unasyn (ampicillin/sulbactam) is a combination product. Note: Dosage recommendations are expressed as grams of ampicillin/sulbactam combination.
Susceptible infections: IM, IV: 1.5 to 3 g every 6 hours (maximum: 12 g ampicillin/sulbactam daily)
Acute bacterial rhinosinusitis, severe infection requiring hospitalization (off-label use): IV: 1.5 to 3 g every 6 hours for 5 to 7 days (Chow 2012)
Amnionitis, cholangitis, diverticulitis, endomyometritis (with doxycycline), endophthalmitis, epididymitis/orchitis, liver abscess (with metronidazole), or peritonitis: IV: 3 g every 6 hours
Bite wounds (animal/human) (off-label use): IV: 1.5 to 3 g every 6 hours (human bites) or every 6 to 8 hours (animal bites) (IDSA [Stevens 2014])
Endocarditis, treatment (off-label use): Enterococcus (native or prosthetic valve; beta-lactamase producing strains resistant to penicillin/susceptible to aminoglycoside and vancomycin): IV: 3 g every 6 hours with a concomitant aminoglycoside for 6 weeks (AHA [Baddour 2015])
Intravascular catheter-associated bloodstream infection, Acinetobacter spp (off-label use) (IDSA 2009): IV: 3 g every 6 hours
Orbital cellulitis: IV: 3 g every 6 hours
Osteomyelitis (diabetic foot) (Lipsky 2004): IV: 3 g every 6 hours
Pelvic inflammatory disease (alternative to preferred therapy): IV: 3 g every 6 hours with doxycycline oral or IV; transition from parenteral to oral therapy can usually be initiated within 24 to 48 hours of clinical improvement for a total treatment duration of 14 days; if tubo-ovarian abscess is present, at least 24 hours of inpatient observation is recommended (CDC [Workowski 2015).
Peritonitis associated with CAPD: Intraperitoneal:
Intermittent: 3 g added to one exchange every 12 hours; allow to dwell for at least 6 hours (Blackwell 1990; Li 2010)
Continuous: Loading dose: 1.5 g per liter of dialysate; maintenance dose: 150 mg per liter of dialysate (Li 2010)
Pneumonia, community-acquired (off-label use): IV: 1.5 to 3 g every 6 hours for ≥5 days (Geckler 1994; Majcher-Peszynska 2014; Mandell 2007; Rossoff 1995). Note: In ICU patients, use in combination with azithromycin or a fluoroquinolone (Mandell 2007).
Pneumonia, hospital-acquired or ventilator-associated due to Acinetobacter (off-label use): IV: 3 g every 6 hours (Zalts 2016); duration of therapy is 7 days (may consider shorter or longer duration depending on rate of clinical improvement) (Kalil 2016)
Surgical (perioperative) 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 (Bratzler 2013).
Surgical site infections (intestinal or GI tract) (off-label use): IV: 3 g every 6 hours; in combination with gentamicin or tobramycin (IDSA [Stevens 2014])
Urinary tract infections, pyelonephritis: IV: 3 g every 6 hours for 14 days
Refer to adult dosing.
Unasyn (ampicillin/sulbactam) is a combination product. Note: Dosage recommendations are expressed as mg of the ampicillin component.
Susceptible infections: Children and Adolescents: IV: 100 to 200 mg ampicillin/kg/day divided every 6 hours (maximum: 8 g ampicillin daily or 12 g ampicillin/sulbactam daily).
Epiglottitis: Children and Adolescents: IV: 100 to 200 mg ampicillin/kg/day divided in 4 doses
Intra-abdominal infection, complicated (off-label): 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]).
Endocarditis, treatment (off-label use): 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])
Intravascular catheter-associated bloodstream infection (off-label use) (IDSA 2009): Infants, Children, and Adolescents:
Infants: IV: 100 to 150 mg ampicillin/kg/day in 4 divided doses
Children and Adolescents: IV: 100 to 200 mg ampicillin/kg/day in 4 divided doses
Mild to moderate infections: Children and Adolescents: IV: 100 to 200 mg ampicillin/kg/day divided every 6 hours (maximum: 8 g ampicillin daily or 12 g ampicillin/sulbactam daily)
Peritonsillar and retropharyngeal abscess: Children and Adolescents: IV: 200 mg ampicillin/kg/day in 4 divided doses
Severe infections: Children and Adolescents: IV: 200 mg ampicillin/kg/day divided every 6 hours (maximum: 8 g ampicillin daily or 12 g ampicillin/sulbactam daily)
Surgical (perioperative) prophylaxis (off-label use): Children ≥1 year: IV: 50 mg ampicillin/kg within 60 minutes prior to surgical incision (maximum: 2 g ampicillin or 3 g ampicillin/sulbactam per dose). Doses may be repeated in 2 hours if procedure is lengthy or if there is excessive blood loss (Bratzler 2013).
Dosing: Renal Impairment
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:
CrCl ≥30 mL/minute/1.73 m2: No dosage adjustment necessary.
CrCl 15 to 29 mL/minute/1.73 m2: 1.5 to 3 g every 12 hours
CrCl 5 to 14 mL/minute/1.73 m2: 1.5 to 3 g every 24 hours
End stage renal disease (ESRD) on intermittent hemodialysis (IHD) (administer after hemodialysis on dialysis days): 1.5 to 3 g every 12 to 24 hours (Heintz 2009). Note: Dosing dependent on the assumption of 3 times weekly, complete IHD sessions.
Continuous renal replacement therapy (CRRT): Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug levels in relation to target trough (if appropriate). The following are general recommendations only (based on dialysate flow/ultrafiltration rates of 1 to 2 L/hour and minimal residual renal function) and should not supersede clinical judgment (Heintz 2009; Trotman 2005):
CVVH: Initial: 3 g; maintenance: 1.5 to 3 g every 8 to 12 hours
CVVHD: Initial: 3 g; maintenance: 1.5 to 3 g every 8 hours
CVVHDF: Initial: 3 g; maintenance: 1.5 to 3 g every 6 to 8 hours
Dosing: Hepatic Impairment
There is no dosage adjustment provided in the manufacturer’s labeling.
Direct IV administration and IV infusion: Reconstitute with sterile water for injection (SWFI). Sodium chloride 0.9% (NS) is the diluent of choice for IV infusion use.
IM administration: Reconstitute with SWFI or 0.5% or 2% lidocaine hydrochloride injection.
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.
Some products may contain sodium.
Prior to reconstitution, store at 20°C to 25°C (68°F to 77°F).
IM: Concentration of 375 mg/mL (250 mg ampicillin/125 mg sulbactam) should be used within 1 hour after reconstitution.
Intermittent IV infusion: Solutions made in NS are stable up to 72 hours when refrigerated whereas dextrose solutions (same concentration) are stable for only 4 hours. For stability related to specific concentrations and temperatures, see prescribing information.
Acemetacin: May increase the serum concentration of Penicillins. Monitor therapy
Allopurinol: May enhance the potential for allergic or hypersensitivity reactions to Ampicillin. Monitor therapy
Atenolol: Ampicillin may decrease the bioavailability of Atenolol. Monitor therapy
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy
Chloroquine: May decrease the serum concentration of Ampicillin. Management: Chloroquine prescribing information recommends separating administration of ampicillin and chloroquine by at least 2 hours to minimize any potential negative impact of chloroquine on ampicillin bioavailability. Consider therapy modification
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Avoid combination
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy
Lanthanum: May decrease the serum concentration of Ampicillin. Management: Administer oral ampicillin at least two hours before or after lanthanum. Consider therapy modification
Methotrexate: Penicillins may increase the serum concentration of Methotrexate. 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. Monitor therapy
Probenecid: May increase the serum concentration of Penicillins. Management: Avoid the routine use of penicillins and probenecid, but this combination may be used advantageously in select cases with careful monitoring. Monitor for toxic effects of penicillins if probenecid is initiated or the dose is increased. Consider therapy modification
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. Consider therapy modification
Tetracyclines: May diminish the therapeutic effect of Penicillins. Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Penicillins may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy
May interfere with urinary glucose tests using cupric sulfate (Benedict's solution, Fehling’s solution, or Clinitest®).
Some penicillin derivatives may accelerate the degradation of aminoglycosides in vitro, leading to a potential underestimation of aminoglycoside serum concentration.
Also see Ampicillin.
>10%: Local: Pain at injection site (IM; 16%)
1% to 10%:
Cardiovascular: Thrombophlebitis (3%), phlebitis (1%)
Dermatologic: Skin rash (<2%)
Gastrointestinal: Diarrhea (3%)
Local: Pain at injection site (IV; 3%)
<1%, postmarketing, and/or case reports: Abdominal distention, abdominal pain, acute generalized exanthematous pustulosis, agranulocytosis, anaphylactic shock, anaphylaxis, anemia, angioedema, basophilia, candidiasis, casts in urine (hyaline), chest pain, chills, cholestasis, cholestatic hepatitis, cholestatic jaundice, Clostridium difficile associated diarrhea, constriction of the pharynx, convulsions, decreased hematocrit, decreased hemoglobin, decreased neutrophils, decreased red blood cells, decreased serum albumin, decreased serum total protein, dermatitis, dizziness, drowsiness, dyspepsia, dyspnea, dysuria, edema, eosinophilia, epistaxis, erythema, erythema multiforme, erythrocyturia, exfoliative dermatitis, facial swelling, fatigue, flatulence, gastritis, glossitis, hairy tongue, headache, hemolytic anemia, hepatic insufficiency, hepatitis, hyperbilirubinemia, hypersensitivity reaction, immune thrombocytopenia, increased blood urea nitrogen, increased lactate dehydrogenase, increased liver enzymes, increased monocytes, increased serum alkaline phosphatase, increased serum ALT, increased serum AST, increased serum creatinine, injection site reaction, interstitial nephritis, jaundice, leukopenia, lymphocytopenia, lymphocytosis (abnormal), malaise, melena, mucous membrane bleeding, nausea, positive direct Coombs test, pruritus, pseudomembranous colitis, sedation, Stevens-Johnson syndrome, stomatitis, substernal pain, thrombocythemia, thrombocytopenia, toxic epidermal necrolysis, urinary retention, urticaria, vomiting
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.
• 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.
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.
Pregnancy Risk Factor
Adverse events have not been observed in animal reproduction studies. Both ampicillin and sulbactam cross the placenta. Maternal use of penicillins has generally not resulted in an increased risk of birth defects. When used during pregnancy, pharmacokinetic changes have been observed with ampicillin alone (refer to the Ampicillin monograph for details). Ampicillin/sulbactam may be considered for prophylactic use prior to cesarean delivery (consult current guidelines).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience diarrhea or injection site pain. Have patient report immediately to prescriber vaginal yeast infection, signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes), thrush, or signs of Clostridium difficile (C. diff)-associated diarrhea (abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools) (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
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- Drug class: beta-lactamase inhibitors
Other brands: Unasyn