Ampicillin with Sulbactam

Pharmacologic Category

Antibiotic, Penicillin

Dosing: Adult

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; Gilad 2008; 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 2019a; Baddour 2019b). Duration of treatment for established infection is typically 5 to 14 days (including oral step-down therapy) (Baddour 2019a; Baddour 2019b; 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) have been described (Gilad 2008; 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 2019).

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): 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 2015). Note: Some experts include this combination as a preferred regimen for tubo-ovarian abscess (Beigi 2019).

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 2019; 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: IV: 1.5 to 3 g every 6 hours, generally for 7 days (Bartlett 2019).

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: Targeted therapy for susceptible pathogens: IV: 3 g every 6 hours, in combination with other agent(s) when appropriate, typically for 7 days and individualized based on response to therapy (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) have been described (Assimakopoulos 2019; Gilad 2008; 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).

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment: Adult

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: Adult

There is no dosage adjustment provided in the manufacturer’s labeling.

Dosing: Pediatric

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)

Dosing: Renal Impairment: Pediatric

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.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer’s labeling.

Calculations

• Creatinine Clearance by Cockcroft-Gault
• Creatinine Clearance by Cockcroft-Gault (SI units)
• Creatinine Clearance by Cockcroft-Gault with IBW
• Creatinine Clearance by Cockcroft-Gault with IBW (SI units)
• Creatinine Clearance by Jelliffe
• Creatinine Clearance by Sanaka
• Glomerular Filtration Rate by Abbreviated MDRD
• Glomerular Filtration Rate by Abbreviated MDRD (SI units)
• Glomerular Filtration Rate by MDRD
• Glomerular Filtration Rate by MDRD (IDMS-Traceable SCr)
• Glomerular Filtration Rate by MDRD (SI units)
• Glomerular Filtration Rate by Schwartz
• Glomerular Filtration Rate Estimate in African Americans by AASK Equation

Use: Labeled Indications

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.

* See Uses in AHFS Essentials for additional information.

Use: Off-Label: Adult

Bite wound infection, treatment (animal or human bite)Level of Evidence [G]

Based on the Infectious Diseases Society of America (IDSA) guidelines for the diagnosis and management of skin and soft tissue infections (SSTIs), ampicillin/sulbactam is an effective and recommended treatment for bite wounds.

Bloodstream infectionLevel of Evidence [C, G]

Data from a retrospective study Ref and a prospective observational study Ref suggest that ampicillin/sulbactam may be beneficial for the treatment of bloodstream infection caused by Acinetobacter spp.

Based on the IDSA guidelines for the diagnosis and management of intravascular catheter-related infection, ampicillin/sulbactam is an effective and recommended treatment for infection with susceptible organisms (eg, Acinetobacter spp.).

Endocarditis, treatmentLevel of Evidence [G]

Based on the American Heart Association scientific statement on infective endocarditis in adults, ampicillin/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.

Odontogenic infection, pyogenicLevel of Evidence [C]

Clinical experience suggests the utility of ampicillin/sulbactam for the treatment of pyogenic odontogenic infection Ref.

PneumoniaLevel of Evidence [C, G]

Data from a multicenter, prospective, noncomparative, open-label clinical pharmacokinetic study in patients with community-acquired pneumonia (CAP) support 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 CAP studies) based on pharmacokinetic analyses in vivo Ref. 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 Ref. Of note, the definition of clinical cure, improvement, and failure in this study were subjective.

Based on the American Thoracic Society (ATS) and IDSA guidelines on the diagnosis and treatment of adults with CAP, ampicillin/sulbactam is effective and recommended for the empiric treatment of CAP in the inpatient setting in adults that do not have risk factors for Pseudomonas aeruginosa. Based on the IDSA and ATS guidelines for the management of adults with hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), ampicillin/sulbactam is effective and recommended for the treatment of HAP or VAP caused by susceptible Acinetobacter spp.

Surgical prophylaxisLevel of Evidence [G]

Based on the American Society of Health-System Pharmacists, IDSA, Surgical Infection Society, and Society for Healthcare Epidemiology of America guidelines for antimicrobial prophylaxis in surgery, ampicillin/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, plastic surgery).

Surgical site infections (eg, intestinal, GU tract, abdominal wall)Level of Evidence [G]

Based on the IDSA guidelines for the diagnosis and management of SSTIs, 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 GU 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).

Level of Evidence Definitions

Level of Evidence Scale

Class and Related Monographs

Penicillins

Clinical Practice Guidelines

Diabetic Foot Infection:

IDSA, “The Diagnosis and Treatment of Diabetic Foot Infections,” 2012

Infective Endocarditis:

AHA, “Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications,” October 2015

Intravascular Catheter-Related Infection:

IDSA, “Clinical Practice Guidelines for the Diagnosis and Management of Intravascular Catheter-Related Infection: 2009 Update,” 2009

Pneumonia, Community-Acquired

ATS/IDSA, "Diagnosis and Treatment of Adults With Community-Acquired Pneumonia," 2019

Pneumonia, Hospital-Acquired and Ventilator-Associated:

IDSA/ATS, "Management of Adults with Hospital-Acquired and Ventilator-Associated Pneumonia," July 2016

Rhinosinusitis:

IDSA, “Clinical Practice Guideline for Acute Bacterial Rhinosinusitis in Children and Adults,” 2012

Sexually Transmitted Disease:

CDC, “Sexually Transmitted Diseases Treatment Guidelines,” June 2015

Public Health Agency of Canada, “Canadian Guidelines on Sexually Transmitted Infections,” January 2010

Skin and Soft-tissue Infection:

IDSA, “Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections,” June 2014

Surgical Prophylaxis:

ASHP, “Clinical Practice Guidelines for Antimicrobial Prophylaxis in Surgery,” February 2013

Administration: IM

Administer around-the-clock to promote less variation in peak and trough serum levels. 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.

Administration: IV

Administer around-the-clock to promote less variation in peak and trough serum levels. 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.

Administration: Injectable Detail

pH: 8 to 10

Administration: Pediatric

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.

Dietary Considerations

Some products may contain sodium.

Storage/Stability

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: Refer to manufacturer's labeling for specific storage instructions after reconstitution and dilution (varies by concentration and diluent).

Preparation for Administration: Adult

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.

Preparation for Administration: Pediatric

IM: Reconstitute with SWFI or lidocaine (0.5% or 2%) to a final concentration of 375 mg/mL of Unasyn (ie, 250 mg/mL of ampicillin and 125 mg/mL of sulbactam). Administer within 1 hour of preparation.

IV: Use within several hours after preparation. Reconstitute with SWFI. Further dilute with a compatible solution; sodium chloride 0.9% (NS) is the diluent of choice for IV piggyback use; final concentration should not exceed 45 mg/mL Unasyn (30 mg/mL of ampicillin and 15 mg/mL of sulbactam)

Compatibility

See Trissel’s IV Compatibility Database

Open Trissel's IV Compatibility

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to treat bacterial infections.

Frequently reported side effects of this drug

• Diarrhea

• Injection site pain

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.

• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes.

• Clostridioides (formerly Clostridium) difficile-associated diarrhea like abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools.

• Signs of a significant reaction like 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. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Contraindications

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

Warnings/Precautions

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.

* See Cautions in AHFS Essentials for additional information.

Geriatric Considerations

Adjust dose for renal function.

Pregnancy Considerations

Both ampicillin and sulbactam cross the placenta.

Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of ampicillin/sulbactam may be altered (Chamberlain 1993). Ampicillin/sulbactam may be considered for prophylactic use prior to cesarean delivery (consult current recommendations) (ACOG 199 2018).

Breast-Feeding Considerations

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 women. 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.

Lexicomp Pregnancy & Lactation, In-Depth

• Ampicillin and Sulbactam

Briggs' Drugs in Pregnancy & Lactation

• Ampicillin
• Sulbactam

Adverse Reactions

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, Clostridioides (formerly 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

* See Cautions in AHFS Essentials for additional information.

Allergy and Idiosyncratic Reactions

• Penicillin Allergy

Metabolism/Transport Effects

None known.

Drug Interactions Open Interactions

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

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

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: 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. Risk D: Consider therapy modification

Vitamin K Antagonists (eg, warfarin): Penicillins may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Test Interactions

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.

Monitoring Parameters

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.

Advanced Practitioners Physical Assessment/Monitoring

Assess culture and sensitivity report and patient’s allergy history prior to starting therapy. Obtain CBC with differential, renal function tests (dosage adjustment may be needed), and liver function tests periodically with prolonged therapy. Screen patients for history of renal impairment, liver impairment, or active mononucleosis. Assess for signs of anaphylaxis during first dose. Assess for signs and symptoms of opportunistic infections. Carefully assess any rash that develops during use to differentiate between nonallergic ampicillin rash and hypersensitivity reaction. Assess other medication patient may be taking; alternative therapy or dosage adjustment may be needed. Test for Clostridioides (formerly Clostridium) difficile-associated diarrhea if patient develops diarrhea.

Nursing Physical Assessment/Monitoring

Check ordered labs and report any abnormalities. Monitor patients closely for signs and symptoms of hypersensitivity (shortness of breath, dyspnea, chest pain, complaints of difficulty swallowing or throat tightness, or change in vital signs). Monitor for severe or bloody diarrhea and send a specimen to the lab for Clostridioides (formerly Clostridium) difficile-associated diarrhea. Educate patient to report all rashes that develop during course of antibiotic therapy.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution Reconstituted, Injection:

Generic: 1.5 g: Ampicillin 1 g and sulbactam 0.5 g (1 ea [DSC]); 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)

Anatomic Therapeutic Chemical (ATC) Classification

• J01CR01

Generic Available (US)

Yes

Pricing: US

Solution (reconstituted) (Ampicillin-Sulbactam Sodium Injection)

1.5 (1-0.5) g (per each): $5.04 - $9.54

3 (2-1) g (per each): $7.62 - $19.14

Solution (reconstituted) (Ampicillin-Sulbactam Sodium Intravenous)

1.5 (1-0.5) g (per each): $6.36

3 (2-1) g (per each): $10.92

15 (10-5) g (per each): $47.52 - $90.00

Solution (reconstituted) (Unasyn Injection)

1.5 (1-0.5) g (per each): $9.12

3 (2-1) g (per each): $17.22

Solution (reconstituted) (Unasyn Intravenous)

15 (10-5) g (per each): $86.08

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

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.

Pharmacodynamics/Kinetics

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

Dental Use

Parenteral beta-lactamase-resistant antibiotic combination to treat more severe orofacial infections where beta-lactamase-producing staphylococci and beta-lactamase-producing Bacteroides are present

* See Uses in AHFS Essentials for additional information.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Dental Health Professional Considerations

In maxillary sinus, anterior nasal cavity, and deep neck infections, beta-lactamase-producing staphylococci and beta-lactamase-producing Bacteroides usually are present. In these situations, antibiotics that resist the beta-lactamase enzyme should be administered. Amoxicillin and clavulanic acid is administered orally for moderate infections. Ampicillin sodium and sulbactam sodium (Unasyn) is administered parenterally for more severe infections.

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Rare occurrences of candidiasis, erythema multiforme, facial swelling, glossitis, stomatitis, Stevens-Johnson syndrome, and hairy tongue have been reported.

Effects on Bleeding

No information available to require special precautions

Dental Usual Dosing

Severe orofacial infections: Adults: IM, IV: 1000 to 2000 mg ampicillin (1500 to 3000 mg Unasyn) every 6 hours (maximum: 8 g ampicillin/day, 12 g Unasyn)

Related Information

• Ampicillin

Index Terms

Ampicillin Sodium/Sulbactam Na; Sulbactam and Ampicillin

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Brand Names: International

Aepisul (PH); Ambacitam (TH); Aminoxidin Sulbactam (AR); Ampi-Bis Plus (AR); Ampictam (SY); Ampigen SB (AR); Ampisulcillin (EE); Ampisulvenir (IL); Amplisul (EC); Amsubac (MY, TH); Auropennz (MY); Baccillin (KR); Bactesyn (ID); Begalin-P (GR); Bethacil (IT); Cinam (ID); Demotine (GR); Easyn (MY); Kintamvy (HK); Libractam (PY, UY); Prixin (AR, PY); Rexatam (TH); Rukasyn (KR); Shinasyn (MY); Shu An Xin (CN); Shudi (CN); Sulbacin (KR, PH); Ubacsin (KR); Ubactam (KR); Ultramox (PH); Unacim (FR); Unasyn (EG, IL, UY); Unasyna (CR, DO, GT, HN, NI, PA, SV); Unictam (EG)

Last Updated 5/2/20