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Combination of
AmpicillinPenicillin antibiotic
SulbactamBeta-lactamase inhibitor
Pronunciationam pi sill' in and sul bak' tam
Trade namesUnasyn, Ampictam, others
Clinical data
Drug classAntibiotic[1]
Main usesBacterial infections[2]
Side effectsPain at site of injection, diarrhea, nausea, rash[2]
  • US: B (No risk in non-human studies)
Routes of
Intramuscular, intraveneous
External links
Legal status

Ampicillin/sulbactam, sold under the brand name Unasyn among others, is an antibiotic used to treat bacterial infections.[2] This includes joint infections, intra abdominal infections, endometritis, pneumonia, skin infections including those caused by animal bites, and meningitis.[2] It is given by injection into a vein or muscle.[2]

Common side effects include pain at the site of injection, diarrhea, nausea, and rash.[2] Other side effects may include anaphylaxis, liver problems, Stevens-Johnson syndrome, and Clostridioides difficile infection.[1] While there is no evidence of harm with use in pregnancy, such use has not been well studied.[1] It is a combination medication of the antibiotic ampicillin and the beta-lactamase inhibitor sulbactam.[1]

The combination was approved for medical use in the United States in 1986.[2] It is available as a generic medication.[2] In the United States 10 doses of 1.5 grams costs about 23 USD as of 2022.[4] It is also avaliable in some countries as the modified form known as sultamicillin, which can be taken by mouth.[5]

Medical uses

Ampicillin/sulbactam has a wide array of medical use for many different types of infectious disease. It is usually reserved as a second-line therapy in cases where bacteria have become beta-lactamase resistant, rendering traditional penicillin-derived antibiotics ineffective. It is effective against certain gram positive bacteria, gram-negative bacteria, and anaerobes.[6]

  • Gram-positive bacteria: Staphylococcus aureus (beta-lactamase and non-beta-lactamase producing), Staphylococcus epidermidis (beta-lactamase and non-beta-lactamase producing), Staphylococcus saprophyticus (beta-lactamase and non-beta-lactamase producing), Streptococcus faecalis (Enterococcus), Streptococcus pneumoniae, Streptococcus pyogenes, and Streptococcus viridans.[6][7]
  • Gram-negative bacteria: Hemophilus influenzae (beta-lactamase and non-beta-lactamase producing), Moraxella (Branhamella) catarrhalis (beta-lactamase and non-beta-lactamase producing), Escherichia coli (beta-lactamase and non-beta-lactamase producing), Klebsiella species (all known species are beta-lactamase producing), Proteus mirabilis (beta-lactamase and non-beta-lactamase producing), Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Morganella morganii, and Neisseria gonorrhoeae (beta-lactamase and non-beta-lactamase producing).[6][7]
  • Anaerobes: Clostridium species, Peptococcus species, Peptostreptococcus species, Bacteroides species including B. fragilis.[6][7]


Ampicillin/sulbactam can be used to treat gynecological infections caused by beta-lactamase producing strains of Escherichia coli, and Bacteroides (including B. fragilis).[6][8]

Bone and joint

Ampicillin/sulbactam can be used in the treatment of bone and joint infections caused by susceptible beta-lactamase producing bacteria.[9][10][11][12]


Ampicillin/sulbactam can be used to treat intra-abdominal infections caused by beta-lactamase producing strains of Escherichia coli, Klebsiella (including K. pneumonia), Bacteroides fragilis, and Enterobacter.[6][8]

Skin infections

This medication can be used to treat skin and skin structure infections caused from beta-lactamase-producing strains of Staphylococcus aureus, Enterobacter, Escherichia coli, Klebsiella (including K. pneumoniae), Proteus mirabilis, Bacteroides fragilis, and Acinetobacter calcoaceticus.[6][8] Examples of skin conditions treated with ampicillin-sulbactam are moderate to severe diabetic foot infections and type 1 Necrotizing fasciitis, commonly referred to as "flesh-eating bacteria".[13]


It may be used at a dose of 1.5 to 3 grams every 6 hours.[2]


Ampicillin/sulbactam is contraindicated in individuals who have a history of a penicillin allergy. Symptoms of allergic reactions may range from rash to potentially life-threatening conditions, such as anaphylaxis. Patients who have asthma, eczema, hives, or hay fever are more likely to develop undesirable reactions to any of the penicillins.[14]

Side effects

Side effects include both local and systemic reactions. Local adverse reactions are characterized by redness, tenderness, and soreness of the skin at the injection site. The most common local reaction is injection site pain. It has been reported to occur in 16% of patients receiving intramuscular injections, and 3% of patients receiving intravenous injections. Less frequently reported side effects include inflammation of veins (1.2%), sometimes associated with a blood clot (3%). The most commonly reported systemic reactions are diarrhea (3%) and rash (2%).[14][15] Less frequent systemic reactions to ampicillin/sulbactam include chest pain, fatigue, seizure, headache, painful urination, urinary retention, intestinal gas, nausea, vomiting, itching, hairy tongue, tightness in throat, reddening of the skin, nose bleeding, and facial swelling. These are reported to occur in less than 1% of patients.[14][15][16]


The addition of sulbactam to ampicillin enhances the effects of ampicillin. This increases the antimicrobial activity by 4- to 32-fold when compared to ampicillin alone.[17] Ampicillin is a time-dependent antibiotic. Its bacterial killing is largely related to the time that drug concentrations in the body remain above the minimum inhibitory concentration (MIC). The duration of exposure will thus correspond to how much bacterial killing will occur. Various studies have shown that, for maximum bacterial killing, drug concentrations must be above the MIC for 50-60% of the time for the penicillin group of antibiotics. This means that longer durations of adequate concentrations are more likely to produce therapeutic success. However, when ampicillin is given in combination with sulbactam, regrowth of bacteria has been seen when sulbactam levels fall below certain concentrations. As with many other antibiotics, under-dosing of ampicillin/sulbactam may lead to resistance.[18]

Ampicillin/sulbactam has poor absorption when given orally.[17] The two drugs have similar pharmacokinetic profiles that appear unchanged when given together. Ampicillin and sulbactam are both hydrophilic antibiotics and have a volume of distribution (Vd) similar to the volume of extra-cellular body water. The volume that the drug distributes throughout in healthy patients is approximately 0.2 liters per kilogram of body weight. Patients on hemodialysis, elderly patients, and pediatric patients have shown a slightly increased volume of distribution. Using typical doses, ampicillin/sulbactam has been shown to reach desired levels to treat infections in the brain, lungs, and abdominal tissues.[18] Both agents have moderate protein binding, reported at 38% for sulbactam and 28% for ampicillin.15,16 The half-life of ampicillin is approximately 1 hour, when used alone or in combination with sulbactam; therefore it will be completely eliminated from a healthy person in around 5 hours. It is eliminated primarily by the urinary system, with 75% excreted unchanged in the urine. Only small amounts of each drug were found to be excreted in the bile.[18] Ampicillin/sulbactam should be given with caution in infants less than a week old and premature neonates. This is due to the underdeveloped urinary system in these patients, which can cause a significantly increased half-life for both drugs.16 Based on its elimination, ampicillin/sulbactam is typically given every 6 to 8 hours. Slowed clearance of both drugs has been seen in the elderly, renal disease patients, and critically ill patients on renal replacement therapy. Reduced clearance has been seen in both pediatric and post-operative patients. Adjustments in dosing frequency may be required in these patients due to these changes.[18]

Mechanism of action

Ampicillin/sulbactam is a combination of a β-lactam antibiotic and a β-lactamase inhibitor. Ampicillin works by binding to penicillin-binding proteins (PBPs) to inhibit bacterial cell wall synthesis.[17][18] This causes disruption of the bacterial cell wall and leads to bacterial cell death. However, resistant pathogens may produce β-lactamase enzymes that can inactivate ampicillin through hydrolysis.[18] This is prevented by the addition of sulbactam, which binds and inhibits the β-lactamase enzymes.[17][18] It is also capable of binding to the PBP of Bacteroides fragilis and Acinetobacter spp., even when it is given alone. The activity of sulbactam against Acinetobacter spp. seen in in-vitro studies makes it distinctive compared to other β-lactamase inhibitors, such as tazobactam and clavulanic acid.[18]


Ampicillin sodium is derived from the basic penicillin nucleus, 6-aminopenicillanic acid. Its chemical name is monosodium (2S, 5R, 6R)-6-[(R)-2-amino-2-phenylacetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate. It has a molecular weight of 371.39 grams and its chemical formula is C16H18N3NaO4S.[6] Sulbactam sodium is also a derivative of 6-aminopenicillanic acid. Chemically, it is known as either sodium penicillinate sulfone or sodium (2S, 5R)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate 4,4-dioxide. It has a molecular weight of 255.22 grams and its chemical formula is C8H10NNaO5S.[6]

Skeletal formula of ampicillin Skeletal formula of sulbactam Skeletal formula of sultamicillin, highlighting ampicillin in blue and sulbactam in red

Ampicillin/sulbactam is also used when the cause of an infection is not known (empiric therapy), such as intra-abdominal infections, skin infections, pneumonia, and gynecologic infections. It is active against a wide range of bacterial groups, including Staphylococcus aureus, Enterobacteriaceae, and anaerobic bacteria. Importantly, it is not active against Pseudomonas aeruginosa and should not be used alone when infection with this organism is suspected or known.


The introduction and use of ampicillin alone started in 1961.[19] The development and introduction of this drug allowed the use of targeted therapies against gram-negative bacteria. With the rise of beta-lactamase producing bacteria, ampicillin and the other penicillin-derivatives became ineffective to these resistant organisms. With the introduction of beta-lactamase inhibitors such as sulbactam, combined with ampicillin made beta-lactamase producing bacteria susceptible.[20]

Society and culture


  • Unasyn (US)
  • Subacillin (Taiwan)
  • Unictam (Egypt)
  • Ultracillin (Egypt)
  • Fortibiotic
  • Sulbin (Egypt)
  • Novactam (Egypt)
  • Sulbacin (Kenya[21])


Ampicillin-sulbactam only comes in a parenteral formulation to be either used as intravenous or intramuscular injections, and can be formulated for intravenous infusion.[6][22] It is formulated in a 2:1 ratio of ampicillin:sulbactam. The commercial preparations available include:[22]

  • 1.5 grams (1 gram ampicillin and 0.5 gram sulbactam)

→Brand names: Unasyn, Unasyn ADD-Vantage, Unasyn Piggyback

  • 3 grams (2 grams ampicillin and 1 gram sulbactam)

→Brand names: Unasyn, Unasyn ADD-Vantage, Unasyn Piggyback

  • 15 grams (10 grams ampicillin and 5 grams sulbactam)

→Brand name: Unasyn


  1. 1.0 1.1 1.2 1.3 "DailyMed - AMPICILLIN AND SULBACTAM- ampicillin sodium and sulbactam sodium injection, powder, for solution". Archived from the original on 24 November 2021. Retrieved 14 January 2022.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 "Ampicillin/Sulbactam Monograph for Professionals". Archived from the original on 25 January 2021. Retrieved 14 January 2022.
  3. "Unasyn- ampicillin sodium and sulbactam sodium injection, powder, for solution". DailyMed. 17 October 2019. Archived from the original on 5 November 2021. Retrieved 12 October 2020.
  4. "Ampicillin/sulbactam Prices, Coupons & Patient Assistance Programs". Retrieved 14 January 2022.
  5. Friedel, Heather A.; Campoli-Richards, Deborah M.; Goa, Karen L. (April 1989). "Sultamicillin: A Review of its Antibacterial Activity, Pharmacokinetic Properties and Therapeutic Use". Drugs. 37 (4): 491–522. doi:10.2165/00003495-198937040-00005. PMID 2661196.
  6. 6.0 6.1 6.2 6.3 6.4 6.5 6.6 6.7 6.8 6.9 Pamphlet Pfizer. Unasyn® (ampicillin sodium/sulbactam sodium) prescribing information. New York, NY; Updated May 2014.
  7. 7.0 7.1 7.2 Clinical and Laboratory Standard Institute (CLSI). Performance Standards for Antimicrobial Disk Diffusion Susceptibility Tests; Approved Standard – 11th ed. CLSI document M02-A11. CLSI, 950 West Valley Rd., Suite 2500, Wayne, PA 19087, 2012.
  8. 8.0 8.1 8.2 Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; 22nd Supplement. CLSI document M100-S22, 2012.>
  9. Campoli-Richards, Deborah M.; Brogden, Rex N. (June 1987). "Sulbactam/Ampicillin: A Review of its Antibacterial Activity, Pharmacokinetic Properties, and Therapeutic Use". Drugs. 33 (6): 577–609. doi:10.2165/00003495-198733060-00003. PMID 3038500. S2CID 209140985.
  10. Löffler, L.; Bauernfeind, A.; Keyl, W.; Hoffstedt, B.; Piergies, A.; Lenz, W. (1 November 1986). "An Open, Comparative Study of Sulbactam plus Ampicillin vs. Cefotaxime as Initial Therapy for Serious Soft Tissue and Bone and Joint Infections". Clinical Infectious Diseases. 8 (Supplement_5): S593–S598. doi:10.1093/clinids/8.supplement_5.s593. PMID 3026009.
  11. Aronoff, Stepben C.; Scoles, Peter V.; MakJey, Jobn T.; Jacobs, Micbael R.; Blumer, Jeffrey L.; Kalamchi, Ali (1 November 1986). "Efficacy and Safety of Sequential Treatment with Parenteral Sulbactam/Ampicillin and Oral Sultamicillin for Skeletal Infections in Children". Clinical Infectious Diseases. 8 (Supplement_5): S639–S643. doi:10.1093/clinids/8.supplement_5.s639. PMID 3026018.
  12. Löffler, L.; Bauernfeind, A.; Keyl, W. (1988). "Sulbactam/Ampicillin versus Cefotaxime as Initial Therapy in Serious Soft Tissue, Joint and Bone Infections". Drugs. 35 (Supplement 7): 46–52. doi:10.2165/00003495-198800357-00012. PMID 3265378. S2CID 29850810.
  13. Fish, Douglas N. (2020). "Skin and Soft-Tissue Infections". Pharmacotherapy: A Pathophysiologic Approach. ISBN 978-1-260-11681-6. Archived from the original on 2021-04-19. Retrieved 2021-06-29.
  14. 14.0 14.1 14.2 Clinical Pharmacology Web site.[permanent dead link]. Accessed November 21, 2014.
  15. 15.0 15.1 UNASYN [package insert]. Pifzer Inc., New York, NY; April 2007. Accessed November 21, 2014.
  16. Unasyn. Lexi-Drugs Online. LexiComp Web Site. Archived 2019-03-06 at the Wayback Machine. Accessed November 21, 2014.
  17. 17.0 17.1 17.2 17.3 Rafailidis PI, Ioannidou EN, Falagas ME (2007). "Ampicillin/Sulbactam Current Status in Severe Bacterial Infections". Drugs. 67 (13): 1829–1849. doi:10.2165/00003495-200767130-00003. PMID 17722953. S2CID 209145407.
  18. 18.0 18.1 18.2 18.3 18.4 18.5 18.6 18.7 Adnan S, Paterson DL, Lipman J, Roberts JA (November 2013). "Ampicillin/sulbactam: its potential use in treating infections in critically ill patients". International Journal of Antimicrobial Agents. 42 (5): 384–389. doi:10.1016/j.ijantimicag.2013.07.012. PMID 24041466.
  19. Acred, P.; Brown, D. M.; Turner, D. H.; Wilson, M. J. (April 1962). "Pharmacology and chemotherapy of ampicillin-a new broad-spectrum penicillin". British Journal of Pharmacology and Chemotherapy. 18 (2): 356–369. doi:10.1111/j.1476-5381.1962.tb01416.x. PMC 1482127. PMID 13859205.
  20. Aronoff, S C; Jacobs, M R; Johenning, S; Yamabe, S (1 October 1984). "Comparative activities of the beta-lactamase inhibitors YTR 830, sodium clavulanate, and sulbactam combined with amoxicillin or ampicillin". Antimicrobial Agents and Chemotherapy. 26 (4): 580–582. doi:10.1128/aac.26.4.580. PMC 179968. PMID 6097169.
  21. "Archive copy". Archived from the original on 2021-07-19. Retrieved 2021-06-29.{{cite web}}: CS1 maint: archived copy as title (link)
  22. 22.0 22.1 Unasyn. DynaMed Web Site.[verification needed]

External links