Tigecycline (
INNAn International Nonproprietary Name is the official non-proprietary or generic name given to a pharmaceutical substance, as designated by the World Health Organization...
) is an
glycylcyclineGlycylcyclines are a new class of antibiotics derived from tetracycline. These tetracycline analogues are specifically designed to overcome two common mechanisms of tetracycline resistance, namely resistance mediated by acquired efflux pumps and/or ribosomal protection...
antibioticIn common usage, an antibiotic is a substance or compound that kills or inhibits the growth of bacteria...
developed and marketed by
WyethWyeth, formerly known as American Home Products , was one of the largest pharmaceutical companies in the world. The company is based in Madison, New Jersey...
under the brand name
Tygacil. It was given a U.S.
Food and Drug AdministrationThe Food and Drug Administration is a Government agency of the United States Department of Health and Human Services and is responsible for regulating and supervising the safety of foods, tobacco products, dietary supplements, Medication drugs, vaccines, Biopharmaceutical, blood transfusion,...
(FDA) fast-track approval and was approved on June 17, 2005. It was developed in response to the growing prevalence of
antibiotic resistanceAntibiotic resistance is the ability of a microorganism to withstand the effects of antibiotics. It is a specific type of drug resistance. Antibiotic resistance evolves via natural selection acting upon random mutation, but it can also be engineered by applying an evolutionary stress on a population...
in bacteria such as
Staphylococcus aureusStaphylococcus aureus is the most common cause of staph infections. It is a spherical bacterium, frequently part of the skin flora found in the nose and on skin. About 20% of the population are long-term carriers of S. aureus. S...
.
This antibiotic is the first clinically-available drug in a new class of antibiotics called the glycylcyclines.
Tigecycline (
INNAn International Nonproprietary Name is the official non-proprietary or generic name given to a pharmaceutical substance, as designated by the World Health Organization...
) is an
glycylcyclineGlycylcyclines are a new class of antibiotics derived from tetracycline. These tetracycline analogues are specifically designed to overcome two common mechanisms of tetracycline resistance, namely resistance mediated by acquired efflux pumps and/or ribosomal protection...
antibioticIn common usage, an antibiotic is a substance or compound that kills or inhibits the growth of bacteria...
developed and marketed by
WyethWyeth, formerly known as American Home Products , was one of the largest pharmaceutical companies in the world. The company is based in Madison, New Jersey...
under the brand name
Tygacil. It was given a U.S.
Food and Drug AdministrationThe Food and Drug Administration is a Government agency of the United States Department of Health and Human Services and is responsible for regulating and supervising the safety of foods, tobacco products, dietary supplements, Medication drugs, vaccines, Biopharmaceutical, blood transfusion,...
(FDA) fast-track approval and was approved on June 17, 2005. It was developed in response to the growing prevalence of
antibiotic resistanceAntibiotic resistance is the ability of a microorganism to withstand the effects of antibiotics. It is a specific type of drug resistance. Antibiotic resistance evolves via natural selection acting upon random mutation, but it can also be engineered by applying an evolutionary stress on a population...
in bacteria such as
Staphylococcus aureusStaphylococcus aureus is the most common cause of staph infections. It is a spherical bacterium, frequently part of the skin flora found in the nose and on skin. About 20% of the population are long-term carriers of S. aureus. S...
.
Structure
This antibiotic is the first clinically-available drug in a new class of antibiotics called the glycylcyclines. It is structurally similar to the
tetracyclineTetracycline is a broad-spectrum polyketide antibiotic produced by the Streptomyces genus of Actinobacteria, indicated for use against many bacterial infections. It is a protein synthesis inhibitor. It is commonly used to treat acne today, and more recently, rosacea, and played a historical role...
s in that it contains a central four-ring carbocyclic skeleton and is actually a
derivativeIn calculus the derivative is a measure of how a function changes as its input changes. Loosely speaking, a derivative can be thought of as how much a quantity is changing at a given point; for example, the derivative of the position of a vehicle with respect to time is the instantaneous velocity...
of
minocyclineMinocycline hydrochloride, also known as minocycline, is a broad spectrum tetracycline antibiotic, and has a broader spectrum than the other members of the group. It is a bacteriostatic antibiotic...
. Tigecycline has a substitution at the D-9 position which is believed to confer broad spectrum activity.
Mechanism of action
Tigecycline is bacteriostatic and is a
protein synthesis inhibitorA protein synthesis inhibitor is a substance which stops or slows the growth or proliferation of cells by disrupting the processes that lead directly to the generation of new proteins....
by binding to the 30S ribosomal subunit of bacteria and thereby blocking entry of
Aminoacyl-tRNAAminoacyl-tRNA is tRNA to which its cognated amino acid is adhered. Its role is to deliver the amino acid to the ribosome where it will be incorporated into the polypeptide chain that is being produced...
into the A site of the ribosome during
prokaryotic translationProkaryotic translation is the process by which messenger RNA is translated into proteins in prokaryotes.-Initiation:Initiation of translation in prokaryotes involves the assembly of the components of the translation system which are: the two ribosomal subunits , the mRNA to be translated, the...
.
Indications
Tigecycline is active against many
Gram-positiveGram-positive bacteria are those that are stained dark blue or violet by Gram staining. This is in contrast to Gram-negative bacteria, which cannot retain the crystal violet stain, instead taking up the counterstain and appearing red or pink...
bacteria,
Gram-negativeGram-negative bacteria are those bacteria that do not retain crystal violet dye in the Gram staining protocol. In a Gram stain test, a counterstain is added after the crystal violet, coloring all Gram-negative bacteria with a red or pink color...
bacteria and anaerobes – including activity against
methicillin-resistant Staphylococcus aureusMethicillin-resistant Staphylococcus aureus is a bacterium responsible for difficult-to-treat infections in humans. It may also be referred to as multidrug-resistant Staphylococcus aureus or oxacillin-resistant Staphylococcus aureus...
(MRSA) and multi-drug resistant strains of
Acinetobacter baumanniiAcinetobacter baumannii is a species of pathogenic bacteria called aerobic gram-negative bacillus and is naturally sensitive to relatively few antibiotics. A.baumannii forms opportunistic infections....
. It has no activity against
PseudomonasPseudomonas is a genus of gamma proteobacteria, belonging to the larger family of pseudomonads.Recently, 16S rRNA sequence analysis has redefined the taxonomy of many bacterial species. As a result the genus Pseudomonas includes strains formerly classified in the genera Chryseomonas and Flavimonas...
spp. or
ProteusProteus is a genus of Gram-negative Proteobacteria.-Clinical significance:Three species—P. vulgaris, P. mirabilis, and P. penneri—are opportunistic human pathogens. Proteus includes pathogens responsible for many human urinary tract infections. Proteus mirabilis causes wound and...
spp. The drug is licenced for the treatment of skin and soft tissue infections as well as intra-abdominal infections.
Dosing
Tigecycline is given by slow intravenous infusion (30 to 60 minutes). A single dose of 100 mg is given first, followed by 50 mg every twelve hours after that. Patients with impaired liver function need to be given a lower dose. No adjustment is needed for patients with impaired kidney function. It is not licensed for use in children. There is no oral form available.
Side effects
Tigecycline has similar
side effectIn medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect, and may result from an unsuitable or incorrect dosage or...
s to the
tetracyclineTetracycline is a broad-spectrum polyketide antibiotic produced by the Streptomyces genus of Actinobacteria, indicated for use against many bacterial infections. It is a protein synthesis inhibitor. It is commonly used to treat acne today, and more recently, rosacea, and played a historical role...
s. The most common side effects of tigecycline are diarrhea, nausea and vomiting. Nausea and vomiting is mild or moderate and usually occurs during the first two days of therapy. Other side effects include pain at the injection site, swelling and irritation; increased or decreased heart rate and infections. Also avoid use in children and pregnancy, due to its affects on teeth and bone. As with other antibiotics, overgrowth of organisms that are not susceptible to tigecycline can occur.
External links