Ampicillin and Sulbactam

Pronunciation

(am pi SIL in & SUL bak tam)

U.S. Brand Names

Unasyn®

Synonyms

Sulbactam and Ampicillin

Generic Available

Yes

Canadian Brand Names

Unasyn®

Use

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

Use - Dental

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

Pregnancy Risk Factor

Lactation

Enters breast milk/use caution

Contraindications

Hypersensitivity to ampicillin, sulbactam, penicillins, or any component of the formulations

Warnings/Precautions

Dosage adjustment may be necessary in patients with renal impairment; a low incidence of cross-allergy with other beta-lactams exists; high percentage of patients with infectious mononucleosis have developed rash during therapy with ampicillin. Appearance of a rash should be carefully evaluated to differentiate a nonallergic ampicillin rash from a hypersensitivity reaction. Ampicillin rash occurs in 5% to 10% of children receiving ampicillin 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.

Adverse Reactions

Also see Ampicillin monograph

>10%: Local: Pain at injection site (I.M.)

1% to 10%:

Dermatologic: Rash

Gastrointestinal: Diarrhea

Local: Pain at injection site (I.V.), thrombophlebitis

Miscellaneous: Allergic reaction (may include serum sickness, urticaria, bronchospasm, hypotension, etc)

<1%: Abdominal distension, candidiasis, chest pain, chills, dysuria, edema, epistaxis, erythema, facial swelling, fatigue, flatulence, glossitis, hairy tongue, headache, interstitial nephritis, itching, liver enzymes increased, malaise, mucosal bleeding, nausea, pseudomembranous colitis, seizure, substernal pain, throat tightness, thrombocytopenia, urine retention, vomiting

Overdosage/Toxicology

Symptoms of penicillin overdose include neuromuscular hypersensitivity (eg, agitation, hallucinations, asterixis, encephalopathy, confusion, and seizures). Electrolyte imbalance may occur if the preparation contains potassium or sodium salts, especially in renal failure. Hemodialysis may be helpful to aid in removal of the drug from blood; otherwise, treatment is supportive or symptom-directed.

Drug Interactions

Allopurinol: Theoretically has an additive potential for ampicillin/amoxicillin rash

Aminoglycosides: May be synergistic against selected organisms

Methotrexate: Penicillins may increase the exposure to methotrexate during concurrent therapy; monitor.

Oral contraceptives: Anecdotal reports suggesting decreased contraceptive efficacy with penicillins have been refuted by more rigorous scientific and clinical data.

Probenecid, disulfiram: May increase levels of penicillins (ampicillin)

Warfarin: Effects of warfarin may be increased

Stability

Prior to reconstitution, store at

30°C (86°F).

I.M. and direct I.V. administration: Use within 1 hour after preparation; reconstitute with sterile water for injection or 0.5% or 2% lidocaine hydrochloride injection (I.M.); sodium chloride 0.9% (NS) is the diluent of choice for I.V. piggyback use, solutions made in NS are stable up to 72 hours when refrigerated whereas dextrose solutions (same concentration) are stable for only 4 hours

Compatibility

Stable in NS; variable compatibility (consult detailed reference) in D5¹ /2NS, D5W, LR

Y-site administration: Compatible: Amifostine, aztreonam, cefepime, docetaxel, enalaprilat, etoposide, famotidine, filgrastim, fluconazole, fludarabine, gatifloxacin, gemcitabine, granisetron, heparin, insulin (regular), linezolid, meperidine, morphine, paclitaxel, remifentanil, tacrolimus, teniposide, theophylline, thiotepa. Incompatible: Aminoglycosides (gentamicin, tobramycin), amphotericin B cholesteryl sulfate complex, ciprofloxacin, idarubicin, ondansetron, sargramostim. Variable (consult detailed reference): Cisatracurium, diltiazem, vancomycin

Compatibility when admixed: Compatible: Aztreonam. Incompatible: Aminoglycosides

Mechanism of Action

The addition of sulbactam, a beta-lactamase inhibitor, to ampicillin extends the spectrum of ampicillin to include some beta-lactamase producing organisms; 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.

Pharmacodynamics/Kinetics

Ampicillin: See Ampicillin monograph.

Sulbactam:

Distribution: Bile, blister, and tissue fluids

Protein binding: 38%

Half-life elimination: Normal renal function: 1-1.3 hours

Excretion: Urine (~75% to 85% as unchanged drug) within 8 hours

Dosage

Unasyn® (ampicillin/sulbactam) is a combination product. Dosage recommendations for Unasyn® are based on the ampicillin component.

Children 1 year: I.V.:

Mild-to-moderate infections: 100-150 mg ampicillin/kg/day (150-300 mg Unasyn®) divided every 6 hours; maximum: 8 g ampicillin/day (12 g Unasyn®)

Severe infections: 200-400 mg ampicillin/kg/day divided every 6 hours; maximum: 8 g ampicillin/day (12 g Unasyn®)

Adults: I.M., I.V.: 1-2 g ampicillin (1.5-3 g Unasyn®) every 6 hours; maximum: 8 g ampicillin/day (12 g Unasyn®)

Dosing interval in renal impairment:

Clcr 15-29 mL/minute: Administer every 12 hours

Clcr 5-14 mL/minute: Administer every 24 hours

Administration

Administer around-the-clock to promote less variation in peak and trough serum levels. Administer by slow injection over 10-15 minutes or I.V. over 15-30 minutes. Ampicillin and gentamicin should not be mixed in the same I.V. tubing or administered concurrently.

Monitoring Parameters

With prolonged therapy, monitor hematologic, renal, and hepatic function; monitor for signs of anaphylaxis during first dose

Test Interactions

May interfere with urinary glucose tests using cupric sulfate (Benedict's solution, Clinitest®); may inactivate aminoglycosides in vitro

Dietary Considerations

Sodium content of 1.5 g injection: 115 mg (5 mEq)

Patient Education

Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take any new medication during therapy unless approved by prescriber. This medication is administered by infusion/injection. Report immediately pain, redness, swelling, or burning at injection/infusion site or feelings of acute anxiety, chest tightness, or difficulty swallowing. Maintain adequate hydration (2-3 L/day of fluids) unless instructed to restrict fluid intake. If you have diabetes, drug may cause false test results with Clinitest® urine glucose monitoring; use of another type of glucose monitoring is preferable. May cause diarrhea (if persistent, consult prescriber for approved medication). Report rash or persistent, opportunistic infection (eg, fever, chills, unhealed sores, white plaques in mouth or vagina, purulent vaginal discharge, fatigue). Breast-feeding precaution: Consult prescriber if breast-feeding caution.

Dental Health: Effects on Dental Treatment

Prolonged use of penicillins may lead to development of oral candidiasis.

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Dental Comment

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.

Mental Health: Effects on Mental Status

Large I.V. doses may rarely produce encephalopathy; penicillins have been reported to cause apprehension, illusions, agitation, insomnia, depersonalization, and encephalopathy

Mental Health: Effects on Psychiatric Treatment

Rarely may cause bone marrow suppression; use caution with clozapine and carbamazepine

Dosage Forms

Injection, powder for reconstitution: 3 g [ampicillin sodium 2 g and sulbactam sodium 1 g]; 15 g [ampicillin sodium 10 g and sulbactam sodium 5 g] [bulk package]

Unasyn®: 1.5 g [ampicillin sodium 1 g and sulbactam sodium 0.5 g]; 3 g [ampicillin sodium 2 g and sulbactam sodium 1 g]; 15 g [ampicillin sodium 10 g and sulbactam sodium 5 g] [bulk package]

References

Dajani AS, "Sulbactam/Ampicillin in Pediatric Infections," Drugs , 1988, 35(Suppl 7):35-8.

Donowitz GR and Mandell GL, "Beta-Lactam Antibiotics," N Engl J Med , 1988, 318(7):419-26 and 318(8):490-500.

Goldfarb J, Aronoff SC, Jaffé A, et al, "Sultamicillin in the Treatment of Superficial Skin and Soft Tissue Infections in Children," Antimicrob Agents Chemother , 1987, 31(4):663-4.

Itokazu GS and Danziger LH, "Ampicillin-Sulbactam and Ticarcillin-Clavulanic Acid: A Comparison of Their In Vitro Activity and Review of Their Clinical Efficacy," Pharmacotherapy , 1991, 11(5):382-414.

Kulhanjian J, Dunphy MG, Hamstra S, et al, "Randomized Comparative Study of Ampicillin/Sulbactam vs Ceftriaxone for Treatment of Soft Tissue and Skeletal Infections in Children," Pediatr Infect Dis J , 1989, 8(9):605-10.

Meyers BR, Wilkinson P, Mendelson MH, et al, "Pharmacokinetics of Ampicillin-Sulbactam in Healthy Elderly and Young Volunteers," Antimicrob Agents Chemother , 1991, 35(10):2098-101.

Rho SP, Jones A, Woo M, et al, "Single Dose Pharmacokinetics of Intravenous Ampicillin plus Sulbactam in Healthy Elderly and Young Subjects," J Antimicrob Chemother , 1989, 24(4):573-80.

Syriopoulou V, Bitsi M, Theodoridis C, et al, "Clinical Efficacy of Sulbactam/Ampicillin in Pediatric Infections Caused by Ampicillin-Resistant or Penicillin-Resistant Organisms," Rev Infect Dis , 1986, 8(Suppl 5):630-3.

Wright AJ, "The Penicillins," Mayo Clin Proc , 1999, 74(3):290-307.

Wynn RL and Bergman SA, "Antibiotics and Their Use in the Treatment of Orofacial Infections, Part I and Part II," Gen Dent , 1994, 42(5):398-402, 498-502.

International Brand Names

Unasyn® (CA)

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