Ampicillin/sulbactam

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Ampicillin/sulbactam
Combination of
Ampicillin Penicillin antibiotic
Sulbactam Beta-lactamase inhibitor
Clinical data
Pronunciationam pi sill' in and sul bak' tam
Trade names Unasyn
AHFS/Drugs.com Monograph
MedlinePlus a693021
Routes of
administration 		Intramuscular, intraveneous
ATC code
Legal status
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Identifiers
CAS Number
PubChem CID
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Ampicillin/sulbactam is a fixed-dose combination medication of the common penicillin-derived antibiotic ampicillin and sulbactam, an inhibitor of bacterial beta-lactamase. Two different forms of the drug exist. The first, developed in 1987 and marketed in the United States under the brand name Unasyn, generic only outside the United States, is an intravenous antibiotic. The second, an oral form called sultamicillin, is marketed under the brand name Ampictam outside the United States, and generic only in the United States. Ampicillin/sulbactam is used to treat infections caused by bacteria resistant to beta-lactam antibiotics. Sulbactam blocks the enzyme which breaks down ampicillin and thereby allows ampicillin to attack and kill the bacteria.

Contents

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. [2]

Gynecological Infections
Ampicillin/sulbactam can be used to treat gynecological infections caused by beta-lactamase producing strains of E. coli, and Bacteroides spp. (including B. fragilis). [2] [4]
Bone and joint infections
Ampicillin/sulbactam can be used in the treatment of bone and joint infections caused by susceptible beta-lactamase producing bacteria. [5] [6] [7] [8]
Intra-abdominal infections
Ampicillin/sulbactam can be used to treat intra-abdominal infections caused by beta-lactamase producing strains of E. coli, Klebsiella spp. (including K. pneumonia ), B. fragilis, and Enterobacter spp. [2] [4]
Skin and skin structure Infections
This medication can be used to treat skin and skin structure infections caused from beta-lactamase-producing strains of S. aureus, Enterobacter spp., E. coli, Klebsiella spp. (including K. pneumoniae), P. mirabilis, B. fragilis, and Acinetobacter calcoaceticus . [2] [4] 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". [9]

Contraindications

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. [10]

Adverse effects

Reported adverse events 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%). [10] [11] 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. [10] [11] [12]

Pharmacology

Pharmacodynamics and pharmacokinetics

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. [13] 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. [14]

Ampicillin/sulbactam has poor absorption when given orally. [13] 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. [14] 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 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. [14] 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. [14]

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. [13] [14] 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. [14] This is prevented by the addition of sulbactam, which binds and inhibits the β-lactamase enzymes. [13] [14] 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. [14]

Chemistry

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. [2] 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. [2]

Ampicillin-2D-skeletal.png Sulbactam.svg Sultamicillin schematic.svg
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.

History

The introduction and use of ampicillin alone started in 1961. [15] 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. [16]

Formulation

Ampicillin-sulbactam only comes in a parenteral formulation to be either used as intravenous or intramuscular injections, and can be formulated for intravenous infusion. [2] [17] It is formulated in a 2:1 ratio of ampicillin:sulbactam. The commercial preparations available include: [17]

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

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

→Brand name: Unasyn

Society and culture

Names

Related Research Articles

<span class="mw-page-title-main">Ampicillin</span> Antibiotic

Ampicillin is an antibiotic belonging to the aminopenicillin class of the penicillin family. The drug is used to prevent and treat a number of bacterial infections, such as respiratory tract infections, urinary tract infections, meningitis, salmonellosis, and endocarditis. It may also be used to prevent group B streptococcal infection in newborns. It is used by mouth, by injection into a muscle, or intravenously.

<span class="mw-page-title-main">Beta-lactamase</span> Class of enzymes

Beta-lactamases (β-lactamases) are enzymes produced by bacteria that provide multi-resistance to beta-lactam antibiotics such as penicillins, cephalosporins, cephamycins, monobactams and carbapenems (ertapenem), although carbapenems are relatively resistant to beta-lactamase. Beta-lactamase provides antibiotic resistance by breaking the antibiotics' structure. These antibiotics all have a common element in their molecular structure: a four-atom ring known as a beta-lactam (β-lactam) ring. Through hydrolysis, the enzyme lactamase breaks the β-lactam ring open, deactivating the molecule's antibacterial properties.

<span class="mw-page-title-main">Penicillin</span> Group of antibiotics derived from Penicillium fungi

Penicillins are a group of β-lactam antibiotics originally obtained from Penicillium moulds, principally P. chrysogenum and P. rubens. Most penicillins in clinical use are synthesised by P. chrysogenum using deep tank fermentation and then purified. A number of natural penicillins have been discovered, but only two purified compounds are in clinical use: penicillin G and penicillin V. Penicillins were among the first medications to be effective against many bacterial infections caused by staphylococci and streptococci. They are still widely used today for different bacterial infections, though many types of bacteria have developed resistance following extensive use.

<span class="mw-page-title-main">Methicillin</span> Antibiotic medication

Methicillin (USAN), also known as meticillin (INN), is a narrow-spectrum β-lactam antibiotic of the penicillin class.

<span class="mw-page-title-main">Cephalosporin</span> Class of pharmaceutical drugs

The cephalosporins are a class of β-lactam antibiotics originally derived from the fungus Acremonium, which was previously known as Cephalosporium.

<span class="mw-page-title-main">Aztreonam</span> Chemical compound

Aztreonam, sold under the brand name Azactam among others, is an antibiotic used primarily to treat infections caused by gram-negative bacteria such as Pseudomonas aeruginosa. This may include bone infections, endometritis, intra abdominal infections, pneumonia, urinary tract infections, and sepsis. It is given by intravenous or intramuscular injection or by inhalation.

<span class="mw-page-title-main">Cefazolin</span> Antibiotic medication

Cefazolin, also known as cefazoline and cephazolin, is a first-generation cephalosporin antibiotic used for the treatment of a number of bacterial infections. Specifically it is used to treat cellulitis, urinary tract infections, pneumonia, endocarditis, joint infection, and biliary tract infections. It is also used to prevent group B streptococcal disease around the time of delivery and before surgery. It is typically given by injection into a muscle or vein.

<span class="mw-page-title-main">Piperacillin</span> Antibiotic medication

Piperacillin is a broad-spectrum β-lactam antibiotic of the ureidopenicillin class. The chemical structure of piperacillin and other ureidopenicillins incorporates a polar side chain that enhances penetration into Gram-negative bacteria and reduces susceptibility to cleavage by Gram-negative beta lactamase enzymes. These properties confer activity against the important hospital pathogen Pseudomonas aeruginosa. Thus piperacillin is sometimes referred to as an "anti-pseudomonal penicillin".

<span class="mw-page-title-main">Carbapenem</span> Class of highly effective antibiotic agents

Carbapenems are a class of very effective antibiotic agents most commonly used for treatment of severe bacterial infections. This class of antibiotics is usually reserved for known or suspected multidrug-resistant (MDR) bacterial infections. Similar to penicillins and cephalosporins, carbapenems are members of the beta-lactam antibiotics drug class, which kill bacteria by binding to penicillin-binding proteins, thus inhibiting bacterial cell wall synthesis. However, these agents individually exhibit a broader spectrum of activity compared to most cephalosporins and penicillins. Furthermore, carbapenems are typically unaffected by emerging antibiotic resistance, even to other beta-lactams.

<span class="mw-page-title-main">Cefotaxime</span> Chemical compound

Cefotaxime is an antibiotic used to treat a number of bacterial infections in human, other animals and plant tissue culture. Specifically in humans it is used to treat joint infections, pelvic inflammatory disease, meningitis, pneumonia, urinary tract infections, sepsis, gonorrhea, and cellulitis. It is given either by injection into a vein or muscle.

<span class="mw-page-title-main">Sulbactam</span> Chemical compound

Sulbactam is a β-lactamase inhibitor. This drug is given in combination with β-lactam antibiotics to inhibit β-lactamase, an enzyme produced by bacteria that destroys the antibiotics.

<span class="mw-page-title-main">Sultamicillin</span> Chemical compound

Sultamicillin, sold under the brand name Unasyn among others, is an oral form of the penicillin antibiotic combination ampicillin/sulbactam. It is used for the treatment of bacterial infections of the upper and lower respiratory tract, the kidneys and urinary tract, skin and soft tissues, among other organs. It contains esterified ampicillin and sulbactam.

<span class="mw-page-title-main">Flucloxacillin</span> Penicillin

Flucloxacillin, also known as floxacillin, is an antibiotic used to treat skin infections, external ear infections, infections of leg ulcers, diabetic foot infections, and infection of bone. It may be used together with other medications to treat pneumonia, and endocarditis. It may also be used prior to surgery to prevent Staphylococcus infections. It is not effective against methicillin-resistant Staphylococcus aureus (MRSA). It is taken by mouth or given by injection into a vein or muscle.

<span class="mw-page-title-main">Dicloxacillin</span> Chemical compound

Dicloxacillin is a narrow-spectrum β-lactam antibiotic of the penicillin class. It is used to treat infections caused by susceptible (non-resistant) Gram-positive bacteria. It is active against beta-lactamase-producing organisms such as Staphylococcus aureus, which would otherwise be resistant to most penicillins. Dicloxacillin is available under a variety of trade names including Diclocil (BMS).

<span class="mw-page-title-main">Mezlocillin</span> Chemical compound

Mezlocillin is a broad-spectrum penicillin antibiotic. It is active against both Gram-negative and some Gram-positive bacteria. Unlike most other extended spectrum penicillins, it is excreted by the liver, therefore it is useful for biliary tract infections, such as ascending cholangitis.

<span class="mw-page-title-main">Cefotiam</span> Chemical compound

Cefotiam is a parenteral third-generation cephalosporin antibiotic. It has broad-spectrum activity against Gram-positive and Gram-negative bacteria. As a beta-lactam, its bactericidal activity results from the inhibition of cell wall synthesis via affinity for penicillin-binding proteins.

<span class="mw-page-title-main">Cefoxitin</span> Chemical compound

Cefoxitin is a second-generation cephamycin antibiotic developed by Merck & Co., Inc. from Cephamycin C in the year following its discovery, 1972. It was synthesized in order to create an antibiotic with a broader spectrum. It is often grouped with the second-generation cephalosporins. Cefoxitin requires a prescription and as of 2010 is sold under the brand name Mefoxin by Bioniche Pharma, LLC. The generic version of cefoxitin is known as cefoxitin sodium.

Capnocytophaga is a genus of Gram-negative bacteria. Normally found in the oropharyngeal tract of mammals, they are involved in the pathogenesis of some animal bite wounds and periodontal diseases.

β-Lactamase inhibitor Family of enzymes

Beta-lactamases are a family of enzymes involved in bacterial resistance to beta-lactam antibiotics. In bacterial resistance to beta-lactam antibiotics, the bacteria have beta-lactamase which degrade the beta-lactam rings, rendering the antibiotic ineffective. However, with beta-lactamase inhibitors, these enzymes on the bacteria are inhibited, thus allowing the antibiotic to take effect. Strategies for combating this form of resistance have included the development of new beta-lactam antibiotics that are more resistant to cleavage and the development of the class of enzyme inhibitors called beta-lactamase inhibitors. Although β-lactamase inhibitors have little antibiotic activity of their own, they prevent bacterial degradation of beta-lactam antibiotics and thus extend the range of bacteria the drugs are effective against.

References

  1. ↑ "Unasyn- ampicillin sodium and sulbactam sodium injection, powder, for solution". DailyMed. U.S. National Library of Medicine. 17 October 2019. Retrieved 12 October 2020.
  2. 1 2 3 4 5 6 7 8 9 10 "Unasyn® (ampicillin sodium/sulbactam sodium) prescribing information". New York, NY: Pfizer. May 2014.
  3. 1 2 3 Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard. Vol. 32 (Eleventh ed.). Wayne, PA: Clinical and Laboratory Standard Institute (CLSI). January 2012. CLSI document M02-A11.
  4. 1 2 3 Performance Standards for Antimicrobial Susceptibility Testing (22nd Supplement ed.). Clinical and Laboratory Standards Institute (CLSI). CLSI document M100-S22, 2012.
  5. ↑ Campoli-Richards DM, Brogden RN (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.
  6. ↑ 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". Reviews of Infectious Diseases. 8 (Supplement_5): S593–S598. doi:10.1093/clinids/8.supplement_5.s593. PMID   3026009.
  7. ↑ Aronoff SC, Scoles PV, Makley JT, Jacobs MR, Blumer JL, Kalamchi A (1 November 1986). "Efficacy and safety of sequential treatment with parenteral sulbactam/ampicillin and oral sultamicillin for skeletal infections in children". Reviews of Infectious Diseases. 8 (Supplement_5): S639–S643. doi:10.1093/clinids/8.supplement_5.s639. PMID   3026018.
  8. ↑ 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.
  9. ↑ Fish DN (2020). "Skin and Soft-Tissue Infections". Pharmacotherapy: A Pathophysiologic Approach. McGraw-Hill Education. ISBN   978-1-260-11681-6.
  10. 1 2 3 Peechakara BV, Gupta M (12 October 2022). "Ampicillin/Sulbactam". StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. PMID   30252373.
  11. 1 2 "UNASYN [package insert]". New York, NY: Pifzer Inc. April 2007. Retrieved 21 November 2014.
  12. ↑ "Unasyn". Lexi-Drugs Online. Retrieved 21 November 2014.
  13. 1 2 3 4 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.
  14. 1 2 3 4 5 6 7 8 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.
  15. ↑ Acred P, Brown DM, Turner DH, Wilson MJ (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.
  16. ↑ Aronoff SC, Jacobs MR, Johenning S, Yamabe S (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.
  17. 1 2 "Ampicillin/Sulbactam Drug Monograph". DynaMed. EBSCO Industries, Inc.
  18. ↑ "Ampicillin/Sulbactam". Druglist Kenya. Sulbacin, Unichem Laboratories Ltd.
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