Sultamicillin, sold under the brand name Unasyn among others, is an oral form of the penicillin antibiotic combination

ampicillin/sulbactam 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 ...

. It is used for the treatment of bacterial infections of the upper and lower respiratory tract, the kidneys and

urinary tract The urinary system, also known as the urinary tract or renal system, consists of the kidneys, ureters, bladder, and the urethra. The purpose of the urinary system is to eliminate waste from the body, regulate blood volume and blood pressure, c ...

, skin and

soft tissues Soft tissue is all the tissue in the body that is not hardened by the processes of ossification or calcification such as bones and teeth. Soft tissue connects, surrounds or supports internal organs and bones, and includes muscle, tendons, ligam ...

, among other organs. It contains

ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides a ...

ified

ampicillin Ampicillin is an antibiotic 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 stre ...

and

sulbactam 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. It was patented in 1977 and approved for medical use in ...

. Sultamicillin is better absorbed from the gut than ampicillin/sulbactam, decreasing the chances of

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...

and

dysentery Dysentery (UK pronunciation: , US: ), historically known as the bloody flux, is a type of gastroenteritis that results in bloody diarrhea. Other symptoms may include fever, abdominal pain, and a feeling of incomplete defecation. Complications ...

. The inclusion of sulbactam extends ampicillin's spectrum of action to

beta-lactamase 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 carbap ...

producing strains of bacteria. Oral sulbactam with the intravenous form provides a regimen of continuous sulbactam therapy throughout the treatment, resulting in better clinical results. It was patented in 1979 and approved for medical use in 1987.

Medical uses

Medical uses for sultamicillin include: * Skin and soft tissue infections -

furuncle A boil, also called a furuncle, is a deep folliculitis, which is an infection of the hair follicle. It is most commonly caused by infection by the bacterium ''Staphylococcus aureus'', resulting in a painful swollen area on the skin caused by an ...

carbuncle A carbuncle is a cluster of boils caused by bacterial infection, most commonly with ''Staphylococcus aureus'' or ''Streptococcus pyogenes''. The presence of a carbuncle is a sign that the immune system is active and fighting the infection. The ...

cellulitis Cellulitis is usually a bacterial infection involving the inner layers of the skin. It specifically affects the dermis and subcutaneous fat. Signs and symptoms include an area of redness which increases in size over a few days. The borders of ...

paronychia Paronychia is an inflammation of the skin around the nail, which can occur suddenly, when it is usually due to the bacterium ''Staphylococcus aureus'', or gradually when it is commonly caused by the fungus ''Candida albicans''. The term is fro ...

, impetigo contagiosa,

diabetic foot ulcer Diabetic foot ulcer is a major complication of diabetes mellitus, and probably the major component of the diabetic foot. Wound healing is an innate mechanism of action that works reliably most of the time. A key feature of wound healing is step ...

s and abscesses caused by '' Staphylococcus aureus'' and ''

Streptococcus pyogenes ''Streptococcus pyogenes'' is a species of Gram-positive, aerotolerant bacteria in the genus '' Streptococcus''. These bacteria are extracellular, and made up of non-motile and non-sporing cocci (round cells) that tend to link in chains. They ...

''. *

Upper respiratory tract infection An upper respiratory tract infection (URTI) is an illness caused by an acute infection, which involves the upper respiratory tract, including the nose, sinuses, pharynx, larynx or trachea. This commonly includes nasal obstruction, sore thro ...

s -

pharyngitis Pharyngitis is inflammation of the back of the throat, known as the pharynx. It typically results in a sore throat and fever. Other symptoms may include a Rhinorrhea, runny nose, cough, headache, difficulty swallowing, swollen lymph nodes, and a ...

and

tonsillitis Tonsillitis is inflammation of the tonsils in the upper part of the throat. It can be acute or chronic. Acute tonsillitis typically has a rapid onset. Symptoms may include sore throat, fever, enlargement of the tonsils, trouble swallowing, and en ...

caused by ''

S. pyogenes ''Streptococcus pyogenes'' is a species of Gram-positive, aerotolerant bacteria in the genus ''Streptococcus''. These bacteria are extracellular, and made up of non-motile and non-sporing cocci (round cells) that tend to link in chains. They are ...

'' and ''S. aureus''. Acute and chronic sinusitis caused by ''S. aureus'', '' S. pneumoniae'', '' H. influenzae'' and ''S. progenies''.

Otitis media Otitis media is a group of inflammatory diseases of the middle ear. One of the two main types is acute otitis media (AOM), an infection of rapid onset that usually presents with ear pain. In young children this may result in pulling at the ear, ...

, particularly suppurative otis media, with or without

mastoiditis Mastoiditis is the result of an infection that extends to the air cells of the skull behind the ear. Specifically, it is an inflammation of the mucosal lining of the mastoid antrum and mastoid air cell system inside the mastoid process. The ma ...

antrum. *

Lower respiratory tract infection Lower respiratory tract infection (LRTI) is a term often used as a synonym for pneumonia but can also be applied to other types of infection including lung abscess and acute bronchitis. Symptoms include shortness of breath, weakness, fever, cough ...

s -

bacterial pneumonia Bacterial pneumonia is a type of pneumonia caused by bacterial infection. Types Gram-positive '' Streptococcus pneumoniae'' () is the most common bacterial cause of pneumonia in all age groups except newborn infants. ''Streptococcus pneumonia ...

bronchitis Bronchitis is inflammation of the bronchi (large and medium-sized airways) in the lungs that causes coughing. Bronchitis usually begins as an infection in the nose, ears, throat, or sinuses. The infection then makes its way down to the bronchi. ...

, bronchiectasis caused by ''S. pneumoniae'', ''H. influenzae'', ''Staphylococcus aureus'' and ''S. progenies''. Acute exacerbations of

COPD Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by long-term respiratory symptoms and airflow limitation. The main symptoms include shortness of breath and a cough, which may or may not produce ...

. *

Urinary tract infection A urinary tract infection (UTI) is an infection that affects part of the urinary tract. When it affects the lower urinary tract it is known as a bladder infection (cystitis) and when it affects the upper urinary tract it is known as a kidne ...

s -

pyelonephritis Pyelonephritis is inflammation of the kidney, typically due to a bacterial infection. Symptoms most often include fever and flank tenderness. Other symptoms may include nausea, burning with urination, and frequent urination. Complications may ...

cystitis A urinary tract infection (UTI) is an infection that affects part of the urinary tract. When it affects the lower urinary tract it is known as a bladder infection (cystitis) and when it affects the upper urinary tract it is known as a kidney ...

caused by ''

Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...

'', ''

Proteus mirabilis ''Proteus mirabilis'' is a Gram-negative, facultatively anaerobic, rod-shaped bacterium. It shows swarming motility and urease activity. ''P. mirabilis'' causes 90% of all ''Proteus'' infections in humans. It is widely distributed in soil and ...

'', ''

Klebsiella ''Klebsiella'' is a genus of Gram-negative, oxidase-negative, rod-shaped bacteria with a prominent polysaccharide-based capsule. ''Klebsiella'' species are found everywhere in nature. This is thought to be due to distinct sublineages developi ...

'' and ''Staphylococcus aureus''. * Surgical infections - prophylaxis and treatment of surgical site infections, peri-operative prophylaxis in orthopaedic and cardiovascular surgery. * Gynecological infections - Caused by beta-lactamase producing strains of ''E. coli'' and ''

Bacteroides ''Bacteroides'' is a genus of Gram-negative, obligate anaerobic bacteria. ''Bacteroides'' species are non endospore-forming bacilli, and may be either motile or nonmotile, depending on the species. The DNA base composition is 40–48% GC. Unus ...

'' sp. (including ''

B. fragilis ''Bacteroides fragilis'' is an anaerobic, Gram-negative, pleomorphic to rod-shaped bacterium. It is part of the normal microbiota of the human colon and is generally commensal, but can cause infection if displaced into the bloodstream or surroun ...

''). * Infections of the gastrointestinal tract - Bacterial

esophagitis Esophagitis, also spelled oesophagitis, is a disease characterized by inflammation of the esophagus. The esophagus is a tube composed of a mucosal lining, and longitudinal and circular smooth muscle fibers. It connects the pharynx to the stomach; s ...

, treatment of ''

H. pylori ''Helicobacter pylori'', previously known as ''Campylobacter pylori'', is a gram-negative, microaerophilic, spiral (helical) bacterium usually found in the stomach. Its helical shape (from which the genus name, helicobacter, derives) is thoug ...

'' infections as a part of MDT in ulcer management.

Contraindications

Sultamicillin is contraindicated in people with penicillin allergy and those with

mononucleosis Infectious mononucleosis (IM, mono), also known as glandular fever, is an infection usually caused by the Epstein–Barr virus (EBV). Most people are infected by the virus as children, when the disease produces few or no symptoms. In young adult ...

, as these have an increased risk of developing severe rashes.

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Adverse effects

The most common side effect, as with many other antibiotics, is

diarrhoea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...

and soft stool. In Japanese clinical trials, these occurred with a frequency of 3.7% and 1.1%, respectively; however, in studies outside Japan, diarrhoea was much more common at 10& to over 50% in patients taking sultamicillin. Other adverse effects occurring in the range of 1 to 10% of people include nausea, vomiting, stomach ache, headache, rashes, and infections with ''Candida albicans''. Haemorrhagic colitis caused by ''Clostridium difficile'' infections is a rare complication.

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Interactions

Interactions with other drugs are similar to other penicillins:

allopurinol Allopurinol is a medication used to decrease high blood uric acid levels. It is specifically used to prevent gout, prevent specific types of kidney stones and for the high uric acid levels that can occur with chemotherapy. It is taken by mouth ...

increases the risk for patients to develop rashes. Penicillins slow down the elimination of methotrexate, potentially increasing its adverse effects. Conversely, the elimination of sultamicillin's active constituents (ampicillin and sulbactam) is reduced by

probenecid Probenecid, also sold under the brand name Probalan, is a medication that increases uric acid excretion in the urine. It is primarily used in treating gout and hyperuricemia. Probenecid was developed as an alternative to caronamide to competitive ...

and probably by the nonsteroidal anti-inflammatory drugs (NSAIDs)

aspirin Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...

indometacin Indometacin, also known as indomethacin, is a nonsteroidal anti-inflammatory drug (NSAID) commonly used as a prescription medication to reduce fever, pain, stiffness, and swelling from inflammation. It works by inhibiting the production of pros ...

and

phenylbutazone Phenylbutazone, often referred to as "bute", is a nonsteroidal anti-inflammatory drug (NSAID) for the short-term treatment of pain and fever in animals. In the United States and United Kingdom, it is no longer approved for human use (except in th ...

Pharmacology

Pharmacokinetics

Sultamicillin is a codrug or (mutual prodrug) of ampicillin and sulbactam. After oral intake, it is absorbed and hydrolytically cleaved to ampicillin and sulbactam by

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

s in the gut wall. These two substances are then released into the system in a 1:1 molar ratio. Their pharmacokinetic behaviour is similar (and practically independent of food intake): they reach peak concentrations after about one hour; their

plasma protein binding Plasma protein binding refers to the degree to which medications attach to proteins within the blood. A drug's efficiency may be affected by the degree to which it binds. The less bound a drug is, the more efficiently it can traverse or diffuse t ...

is 26% (ampicillin) and 29% (sulbactam); and their elimination half-lives are 45–80 minutes and 40–70 minutes, respectively. Both drugs are mainly eliminated via the kidneys: within eight hours after intake, 46 to 80% of the ampicillin and 41 to 66% of the sulbactam are found in the urine.

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Mechanism of action

Ampicillin, a

semi-synthetic Semisynthesis, or partial chemical synthesis, is a type of chemical synthesis that uses chemical compounds isolated from natural sources (such as microbial cell cultures or plant material) as the starting materials to produce novel compounds with ...

orally active broad-spectrum penicillin antibiotic, exerts antibacterial activity against sensitive organisms by inhibiting biosynthesis of cell wall mucopeptide. Sulbactam, a

beta-lactamase inhibitor 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 ...

, irreversibly inhibits many

s that occur in resistant bacteria strains.

Chemistry

Ampicillin and sulbactam are linked via a

methylene group In organic chemistry, a methylene group is any part of a molecule that consists of two hydrogen atoms chemical bond, bound to a carbon atom, which is connected to the remainder of the molecule by two single bond, single bonds. The group may be re ...

, forming two

bonds (or more accurately

acylal Acylals in organic chemistry are a group of chemical compounds sharing a functional group with the general structure RCH(OOCR)2. Acylals are obtained by reaction of carbonyls with acetic anhydride or other acid anhydrides and a suitable catalyst, f ...

bonds). Sultamicillin is used in form of the

tosylate In organic chemistry, a toluenesulfonyl group (tosyl group, abbreviated Ts or Tos) is a univalent functional group with the chemical formula –. It consists of a tolyl group, –, joined to a sulfonyl group, ––, with the open valence on s ...

salt.

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References

{{Cell wall disruptive antibiotics Penicillins Codrugs Formals Pfizer brands