Pristinamycin
Encyclopedia
Pristinamycin also spelled pristinamycine, is an antibiotic
used primarily in the treatment of staphylococcal
infections, and to a lesser extent streptococcal
infections. It is a streptogramin
group antibiotic, similar to virginiamycin
, derived from the bacterium Streptomyces pristinaespiralis
. It is marketed in Europe by Sanofi-Aventis
under the trade name Synercid and Pyostacine.
Pristinamycin is a mixture of two components that have a synergistic antibacterial action. Pristinamycin IA
is a macrolide
, and results in pristinamycin having a similar spectrum of action to erythromycin
. Pristinamycin IIA
(streptogramin A) is a depsipeptide
. PI and PII are coproduced by S. pristinaespiralis in a ratio of 30:70. Each compound binds to the bacterial 50 S ribosomal subunit and inhibits the elongation process of the protein synthesis, thereby exhibiting only a moderate bacteriostatic activity. However, the combination of both substances acts synergistically and leads to a potent bactericidal activity that can reach up to 100 times that of the separate components.
The pristinamycin biosynthetic gene cluster is the largest antibiotic supercluster known so far with a size of ~210 kb, where the PI and PII biosynthetic genes are not clustered individually but are scattered across the complete sequence region. Furthermore, this biosynthetic gene region is interrupted by a cryptic type II PKS gene cluster.
(MRSA). Its usefulness for severe infections, however, may be limited by the lack of an intravenous formulation owing to its poor solubility. Nevertheless it is sometimes used as an alternative to rifampicin
+fusidic acid
or linezolid
for the treatment of MRSA.
The lack of an intravenous formulation led to the development of the pristinamycin-derivative quinupristin/dalfopristin
(i.e., Synercid), which may be administered intravenously for more severe MRSA infections.
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
used primarily in the treatment of staphylococcal
Staphylococcus
Staphylococcus is a genus of Gram-positive bacteria. Under the microscope they appear round , and form in grape-like clusters....
infections, and to a lesser extent streptococcal
Streptococcus
Streptococcus is a genus of spherical Gram-positive bacteria belonging to the phylum Firmicutes and the lactic acid bacteria group. Cellular division occurs along a single axis in these bacteria, and thus they grow in chains or pairs, hence the name — from Greek στρεπτος streptos, meaning...
infections. It is a streptogramin
Streptogramin
Streptogramins are a class of antibiotics.Streptogramins are effective in the treatment of vancomycin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus , two of the most rapidly-growing strains of multidrug-resistant bacteria...
group antibiotic, similar to virginiamycin
Virginiamycin
Virginiamycin is a streptogramin antibiotic similar to pristinamycin and quinupristin/dalfopristin. It is a combination of pristinamycin IIA and virginiamycin S1. Virginiamycin is used in the fuel ethanol industry to prevent microbial contamination...
, derived from the bacterium Streptomyces pristinaespiralis
Streptomyces
Streptomyces is the largest genus of Actinobacteria and the type genus of the family Streptomycetaceae. Over 500 species of Streptomyces bacteria have been described. As with the other Actinobacteria, streptomycetes are gram-positive, and have genomes with high guanine and cytosine content...
. It is marketed in Europe by Sanofi-Aventis
Sanofi-Aventis
Sanofi S.A. is a multinational pharmaceutical company headquartered in Paris, France, the world's fourth-largest by prescription sales. Sanofi engages in the research and development, manufacturing and marketing of pharmaceutical products for sale principally in the prescription market, but the...
under the trade name Synercid and Pyostacine.
Pristinamycin is a mixture of two components that have a synergistic antibacterial action. Pristinamycin IA
Pristinamycin IA
Pristinamycin IA is an antibiotic cyclic peptide. It is a member of the streptogramin B group of antibiotics and one component of pristinamycin ....
is a macrolide
Macrolide
The macrolides are a group of drugs whose activity stems from the presence of a macrolide ring, a large macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. The lactone rings are usually 14-, 15-, or 16-membered...
, and results in pristinamycin having a similar spectrum of action to erythromycin
Erythromycin
Erythromycin is a macrolide antibiotic that has an antimicrobial spectrum similar to or slightly wider than that of penicillin, and is often used for people who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including mycoplasma and...
. Pristinamycin IIA
Pristinamycin IIA
Pristinamycin IIA is a macrolide antibiotic. It is a member of the streptogramin A group of antibiotics and one component of pristinamycin ....
(streptogramin A) is a depsipeptide
Depsipeptide
A depsipeptide is a peptide in which one or more of the amide bonds are replaced by ester bonds.Depsipeptides have often been used in research to probe the importance of hydrogen bond networks in protein folding kinetics and thermodynamics. They are also found in nature as natural products...
. PI and PII are coproduced by S. pristinaespiralis in a ratio of 30:70. Each compound binds to the bacterial 50 S ribosomal subunit and inhibits the elongation process of the protein synthesis, thereby exhibiting only a moderate bacteriostatic activity. However, the combination of both substances acts synergistically and leads to a potent bactericidal activity that can reach up to 100 times that of the separate components.
The pristinamycin biosynthetic gene cluster is the largest antibiotic supercluster known so far with a size of ~210 kb, where the PI and PII biosynthetic genes are not clustered individually but are scattered across the complete sequence region. Furthermore, this biosynthetic gene region is interrupted by a cryptic type II PKS gene cluster.
Clinical use
Despite the macrolide component, it is effective against erythromycin-resistant staphylococci and strepcococci. Importantly, it is active against methicillin-resistant Staphylococcus aureusMethicillin-resistant Staphylococcus aureus
Methicillin-resistant Staphylococcus aureus is a bacterium responsible for several difficult-to-treat infections in humans. It is also called multidrug-resistant Staphylococcus aureus and oxacillin-resistant Staphylococcus aureus...
(MRSA). Its usefulness for severe infections, however, may be limited by the lack of an intravenous formulation owing to its poor solubility. Nevertheless it is sometimes used as an alternative to rifampicin
Rifampicin
Rifampicin or rifampin is a bactericidal antibiotic drug of the rifamycin group. It is a semisynthetic compound derived from Amycolatopsis rifamycinica ...
+fusidic acid
Fusidic acid
Fusidic acid is a bacteriostatic antibiotic that is often used topically in creams and eyedrops, but may also be given systemically as tablets or injections...
or linezolid
Linezolid
Linezolid is a synthetic antibiotic used for the treatment of serious infections caused by Gram-positive bacteria that are resistant to several other antibiotics...
for the treatment of MRSA.
The lack of an intravenous formulation led to the development of the pristinamycin-derivative quinupristin/dalfopristin
Quinupristin/dalfopristin
Quinupristin/dalfopristin is a combination of two antibiotics used to treat infections by staphylococci and by vancomycin-resistant Enterococcus faecium....
(i.e., Synercid), which may be administered intravenously for more severe MRSA infections.
See also
- Methicillin-resistant Staphylococcus aureusMethicillin-resistant Staphylococcus aureusMethicillin-resistant Staphylococcus aureus is a bacterium responsible for several difficult-to-treat infections in humans. It is also called multidrug-resistant Staphylococcus aureus and oxacillin-resistant Staphylococcus aureus...
(MRSA) - Quinupristin/dalfopristinQuinupristin/dalfopristinQuinupristin/dalfopristin is a combination of two antibiotics used to treat infections by staphylococci and by vancomycin-resistant Enterococcus faecium....