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Pronunciation
(am pi SIL in & SUL bak tam)
Generic Available (U.S.)
Yes
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
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
B
Pregnancy Considerations
Adverse events have not been observed in animal studies; therefore, ampicillin/sulbactam is classified as pregnancy category B. Both ampicillin and sulbactam cross the placenta. When used during pregnancy, pharmacokinetic changes have been observed with ampicillin alone (refer to the Ampicillin monograph for details).
Lactation
Enters breast milk/use caution
Breast-Feeding Considerations
Ampicillin and sulbactam are both excreted into breast milk in low concentrations. The manufacturer recommends that caution be used if administering to lactating women. Nondose-related effects could include modification of bowel flora and allergic sensitization of the infant. The maternal dose of sulbactam does not need altered in the postpartum period. Also refer to the Ampicillin monograph.
Contraindications
Hypersensitivity to ampicillin, sulbactam, penicillins, or any component of the formulations
Warnings/Precautions
Concerns related to adverse effects:
• Anaphylactoid/hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity, history of sensitivity to multiple allergens, or previous IgE-mediated reactions (eg, anaphylaxis, angioedema, urticaria). Use with caution in asthmatic patients.
• 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:
• Infectious mononucleosis: A high percentage of patients with infectious mononucleosis have developed rash during therapy; ampicillin-class antibiotics not recommended in these patients.
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended.
Adverse Reactions
Also see Ampicillin.
>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
Metabolism/Transport Effects
None known.
Drug Interactions
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: Antibiotics may diminish the therapeutic effect of BCG. Risk X: Avoid combination
Chloroquine: May decrease the serum concentration of Ampicillin. Management: Choroquine 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. Risk D: Consider therapy modification
Fusidic Acid: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification
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 decrease the excretion 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
Tetracycline Derivatives: May diminish the therapeutic effect of Penicillins. Risk D: 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 24 hours 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
Storage
Prior to reconstitution, store at ≤30°C (86°F). Solutions made in NS are stable up to 72 hours when refrigerated whereas dextrose solutions (same concentration) are stable for only 4 hours.
Reconstitution
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.
Compatibility
Stable in NS; variable stability (consult detailed reference) in D51/2NS, D5W, LR.
Y-site administration: Compatible: Amifostine, anidulafungin, aztreonam, bivalirudin, cefepime, dexmedetomidine, docetaxel, enalaprilat, etoposide phosphate, famotidine, fenoldopam, filgrastim, fluconazole, fludarabine, gallium, gemcitabine, granisetron, heparin, hetastarch in lactate electrolyte injection (Hextend®), insulin (regular), linezolid, meperidine, morphine, paclitaxel, palonosetron, pemetrexed, remifentanil, tacrolimus, teniposide, theophylline, thiotepa. Incompatible: Aminoglycosides (gentamicin, tobramycin), amiodarone, amphotericin B cholesteryl sulfate complex, ciprofloxacin, idarubicin, nicardipine, ondansetron. Variable (consult detailed reference): Cisatracurium, diltiazem, drotrecogin alfa, sargramostim, vancomycin.
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.
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
Note: Unasyn® (ampicillin/sulbactam) is a combination product. Dosage recommendations for Unasyn® are based on the ampicillin component.
Usual dosage range:
Children ≥1 year: I.V.: 100-400 mg ampicillin/kg/day divided every 6 hours (maximum: 8 g ampicillin/day, 12 g Unasyn®). Note: The American Academy of Pediatrics recommends a dose of up to 300 mg/kg/day for severe infection in infants >1 month of age.
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®)
Indication-specific dosing:
Children: ≥1 year:
Epiglottitis: I.V.: 100-200 mg ampicillin/kg/day divided in 4 doses
Mild-to-moderate infections: I.V.: 100-200 mg ampicillin/kg/day (150-300 mg Unasyn®) divided every 6 hours (maximum: 8 g ampicillin/day, 12 g Unasyn®)
Peritonsillar and retropharyngeal abscess: I.V.: 50 mg ampicillin/kg/dose every 6 hours
Severe infections: I.V.: 200-400 mg ampicillin/kg/day divided every 6 hours (maximum: 8 g ampicillin/day, 12 g Unasyn®)
Adults: Doses expressed as ampicillin/sulbactam combination:
Amnionitis, cholangitis, diverticulitis, endometritis, endophthalmitis, epididymitis/orchitis, liver abscess, osteomyelitis (diabetic foot), peritonitis: I.V.: 3 g every 6 hours; Note: Due to high rates of E. coli resistance, not recommended for the treatment of community-acquired intra-abdominal infections (Solomkin, 2010)
Endocarditis: I.V.: 3 g every 6 hours with gentamicin or vancomycin for 4-6 weeks
Orbital cellulitis: I.V.: 1.5 g every 6 hours
Parapharyngeal space infections: I.V.: 3 g every 6 hours
Pasteurella multocida
(human, canine/feline bites): I.V.: 1.5-3 g every 6 hours
Pelvic inflammatory disease: I.V.: 3 g every 6 hours with doxycycline
Peritonitis associated with CAPD: Intraperitoneal:
Anuric, intermittent: 3 g every 12 hours (Li, 2010)
Anuric, continuous: Loading dose: 1.5 g per liter of dialysate; maintenance dose: 150 mg per liter of dialysate (Li, 2010)
Pneumonia:
Aspiration, community-acquired: I.V.: 1.5-3 g every 6 hours
Hospital-acquired: I.V.: 3 g every 6 hours
Urinary tract infections, pyelonephritis: I.V.: 3 g every 6 hours for 14 days
Dosing interval in renal impairment: Note: Estimation of renal function for the purpose of drug dosing should be done using the Cockcroft-Gault formula.
Clcr 15-29 mL/minute/1.73 m2: 1.5-3 g every 12 hours
Clcr 5-14 mL/minute/1.73 m2: 1.5-3 g every 24 hours
Intermittent hemodialysis (IHD) (administer after hemodialysis on dialysis days): 1.5-3 g every 12-24 hours (Heintz, 2009). Note: Dosing dependent on the assumption of 3 times/week, complete IHD sessions.
Peritoneal dialysis (PD): 3 g every 24 hours
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 1-2 L/hour and minimal residual renal function) and should not supersede clinical judgment (Heintz, 2009; Trotman, 2005):
CVVH: Initial: 3 g; maintenance: 1.5-3 g every 8-12 hours
CVVHD: Initial: 3 g; maintenance: 1.5-3 g every 8 hours
CVVHDF: Initial: 3 g; maintenance: 1.5-3 g every 6-8 hours
Dental Usual Dosing
Severe orofacial infections: 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®)
Administration: I.V.
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.
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. Concurrent 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 levels, CBC, and clinical response should be considered.
Administration: I.V. Detail
pH: 8-10
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®).
Some penicillin derivatives may accelerate the degradation of aminoglycosides in vitro, leading to a potential underestimation of aminoglycoside serum concentration.
Dietary Considerations
Some products may contain sodium.
Patient Education
See individual agents.
Geriatric Considerations
Adjust dose for renal function.
Dental Health: Effects on Dental Treatment
Prolonged use of penicillins may lead to development of oral candidiasis (see Dental Health Professional Considerations)
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.
Infectious Diseases Comment
A well-documented reaction can occur between beta-lactam and aminoglycoside antibiotics in vitro, leading to complexation, opening of the beta-lactam ring and presumably, loss of antibacterial activity for one or both agents. However, the conditions under which this reaction occurs are variable and influenced by (but not limited to) assay methodology, sampling time and storage, and drug selection and concentration. In general, many of the in vitro studies employed artificial conditions that tested high concentrations of the penicillin derivative (equating to serum levels most likely observed only in severe renal impairment) in combination with gentamicin or tobramycin. Incubation of the agents at conditions of 37°C for up to 48 hours has definitely demonstrated inactivation and loss of bactericidal activity. However, some of these studies permitted a considerable time lapse prior to assaying the medium, or stored the samples at higher temperatures (-20°C or greater), which may have allowed continued chemical degradation prior to assay. In general, amikacin was the most resistant to penicillin-mediated chemical degradation, and cephalosporins were much less likely than penicillins to inactivate the aminoglycosides.
The more robust studies have been those which evaluated in vivo effects via rapid and frequent blood sampling during concomitant dosing. In vivo, there are a number of studies documenting significant changes in the half-life of gentamicin in combination with primarily ticarcillin and carbenicillin, but usually only in the setting of end-stage renal disease. A number of literature reports suggest that despite documented changes in gentamicin kinetics, this is not likely to lead to clinically-significant differences in outcomes in patients with normal renal function. Furthermore, there are no published, prospective, outcomes-based studies that provide compelling evidence of changes in rates of clinical or microbiological response as a function of dosing separation.
Based on the weight of evidence to date, coadministration of (but not coadmixture of) a penicillin or cephalosporin antibiotic with an aminoglycoside should not pose a significant concern in patients with even mild renal impairment. However, specific circumstances exist in which this approach should be undertaken with caution. Concurrent administration of either gentamicin or tobramycin with piperacillin, carbenicillin, or ticarcillin (including combinations with beta-lactamase inhibitors), particularly in the face of moderate-to-severe renal failure, would warrant careful monitoring of aminoglycoside serum levels, CBCs, and clinical response to avoid potentially reduced efficacy due to chemical inactivation.
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
Nursing: Physical Assessment/Monitoring
See individual agents.
Dosage Forms
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
Unasyn®:
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)]
References
Blum RA, Kohli RK, Harrison NJ, et al, “Pharmacokinetics of Ampicillin (2.0 Grams) and Sulbactam (1.0 Gram) Coadministered to Subjects With Normal and Abnormal Renal Function and With End-Stage Renal Disease on Hemodialysis,” Antimicrob Agents Chemother, 1989, 33(9):1470-6.
Centers for Disease Control and Prevention, “Sexually Transmitted Diseases Treatment Guidelines, 2006,” MMWR, 2006, 55(RR-11): 1-94.
Chow MS, Quintiliani R, and Nightingale CH, “In Vivo Inactivation of Tobramycin by Ticarcillin. A Case Report,” JAMA, 1982, 247(5):658-9.
Dajani AS, “Sulbactam/Ampicillin in Pediatric Infections,” Drugs, 1988, 35(Suppl 7):35-8.
Daly JS, Dodge RA, Glew RH, et al, “Effect of Time and Temperature on Inactivation of Aminoglycosides by Ampicillin at Neonatal Dosages," J Perinatol, 1997, 17(1):42-5.
Donowitz GR and Mandell GL, “Beta-Lactam Antibiotics,” N Engl J Med, 1988, 318(7):419-26 and 318(8):490-500.
Dowell JA, Korth-Bradley J, Milisci M, et al, “Evaluating Possible Pharmacokinetic Interactions Between Tobramycin, Piperacillin, and a Combination of Piperacillin and Tazobactam in Patients With Various Degrees of Renal Impairment,” J Clin Pharmacol, 2001, 41:979-86.
Farchione LA, “Inactivation of Aminoglycosides by Penicillins,” J Antimicrob Chemother, 1982, 8(Suppl A):27-36.
Fuchs PC, Stickel S, Anderson PH, et al, “In Vitro Inactivation of Aminoglycosides by Sulbactam, Other Beta-Lactams, and Sulbactam-Beta-Lactam Combinations,” Antimicrob Agents Chemother, 1991, 35(1):182-4.
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.
Halstenson CE, Wong MO, Herman CS, et al, “Effect of Concomitant Administration of Piperacillin on the Dispositions on Isepamicin and Gentamicin in Patients With End-Stage Renal Disease,” Antimicrob Agents Chemother, 1992, 36(9):1832-36.
Heintz BH, Matzke GR, Dager WE, “Antimicrobial Dosing Concepts and Recommendations for Critically Ill Adult Patients Receiving Continuous Renal Replacement Therapy or Intermittent Hemodialysis,” Pharmacotherapy, 2009, 29(5):562-77.
Hitt CM, Patel KB, Nicolau DP, et al, “Influence of Piperacillin-Tazobactam on Pharmacokinetics of Gentamicin Given Once Daily,” Am J Health Syst Pharm, 1997, 54(23):2704-8.
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.
Konishi H, Goto M, Nakamoto Y, et al, “Tobramycin Inactivation by Carbenicillin, Ticarcillin, and Piperacillin,” Antimicrob Agents Chemother, 1983, 23(5):653-57.
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.
Lau A, Lee M, Flascha S, et al, “Effect of Piperacillin on Tobramycin Pharmacokinetics in Patients With Normal Renal Function,” Antimicrob Agents Chemother, 1983, 24(4):533-37.
Li PK, Szeto CC, Piraino B, et al, "Peritoneal Dialysis-Related Infections Recommendations: 2010 Update," Perit Dial Int, 2010, 30(4):393-423
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Solomkin JS, Mazuski JE, Bradley JS, et al, “Diagnosis and Management of Complicated Intra-Abdominal Infections in Adults and Children: Guidelines by the Surgical Infection Society and the Infectious Diseases Society of America,” Clin Infect Dis, 2010, 50(2):133-64.
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Trotman RL, Williamson JC, Shoemaker DM, et al, “Antibiotic Dosing in Critically Ill Adult Patients Receiving Continuous Renal Replacement Therapy,” Clin Infect Dis, 2005, 41(8):1159-66.
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Wright AJ, “The Penicillins,” Mayo Clin Proc, 1999, 74(3):290-307.
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International Brand Names
Lexi-Comp.com
Last full review/revision January 2012
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