Quinupristin/dalfopristin, or quinupristin-dalfopristin, (pronunciation: kwi NYOO pris tin / dal FOE pris tin) (trade name Synercid) is a combination of two

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy, ...

s used to treat

infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable d ...

s by

staphylococci ''Staphylococcus'' is a genus of Gram-positive bacteria in the family Staphylococcaceae from the order Bacillales. Under the microscope, they appear spherical ( cocci), and form in grape-like clusters. ''Staphylococcus'' species are facultativ ...

and by

vancomycin Vancomycin is a glycopeptide antibiotic medication used to treat a number of bacterial infections. It is recommended intravenously as a treatment for complicated skin infections, bloodstream infections, endocarditis, bone and joint infection ...

-resistant ''

Enterococcus faecium ''Enterococcus faecium'' is a Gram-positive, gamma-hemolytic or non- hemolytic bacterium in the genus '' Enterococcus''. It can be commensal (innocuous, coexisting organism) in the gastrointestinal tract of humans and animals, but it may als ...

''. Quinupristin and dalfopristin are both

streptogramin Streptogramins are a class of antibiotics. Streptogramins are effective in the treatment of vancomycin-resistant ''Staphylococcus aureus'' (VRSA) and vancomycin-resistant ''Enterococcus'' (VRE), two of the most rapidly growing strains of multidru ...

antibiotics, derived from pristinamycin. Quinupristin is derived from pristinamycin IA; dalfopristin from pristinamycin IIA. They are combined in a weight-to-weight ratio of 30% quinupristin to 70% dalfopristin.

Administration

Intravenous, usually 7.5 mg/kg every 8 hours (infections/life threatening VRSA); every 12 hours (skin infections). No renal dosing adjustments, hepatic dosing adjustments are not defined, consider reducing dose.

Mechanism of action

Quinupristin and dalfopristin are

protein synthesis inhibitor A protein synthesis inhibitor is a compound that stops or slows the growth or proliferation of cells by disrupting the processes that lead directly to the generation of new proteins. While a broad interpretation of this definition could be used t ...

s in a synergistic manner. While each of the two is only a

bacteriostatic agent A bacteriostatic agent or bacteriostat, abbreviated Bstatic, is a biological or chemical agent that stops bacteria from reproducing, while not necessarily killing them otherwise. Depending on their application, bacteriostatic antibiotics, disinfec ...

, the combination shows

bactericidal A bactericide or bacteriocide, sometimes abbreviated Bcidal, is a substance which kills bacteria. Bactericides are disinfectants, antiseptics, or antibiotics. However, material surfaces can also have bactericidal properties based solely on their ...

activity. *Dalfopristin binds to the 23S portion of the

50S ribosomal subunit 50 S is the larger subunit of the 70S ribosome of prokaryotes, i.e. bacteria and archaea. It is the site of inhibition for antibiotics such as macrolides, chloramphenicol, clindamycin, and the pleuromutilins. It includes the 5S ribosomal RNA a ...

, and changes the conformation of it, enhancing the binding of quinupristin by a factor of about 100. In addition, it inhibits

peptidyl transfer The peptidyl transferase is an aminoacyltransferase () as well as the primary enzymatic function of the ribosome, which forms peptide bonds between adjacent amino acids using tRNAs during the translation process of protein biosynthesis. The su ...

. *Quinupristin binds to a nearby site on the 50S ribosomal subunit and prevents elongation of the

polypeptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides ...

, as well as causing incomplete chains to be released.

Pharmacokinetics

Clearance by the

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...

CYP450:3A4 inhibitor,

half-life Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable at ...

quinupristin 0.8 hours, dalfopristin 0.7 hours (with persistence of effects for 9–10 hours). Excretion: Quinupristin: 85% feces, 15% urine; Dalfopristin: 81% feces, 19% urine

Side effects

Epocrates v 19.5 Serious: # C.diff-associated diarrhea #superinfection #

anaphylactoid reaction Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the follow ...

s #

angioedema Angioedema is an area of swelling (edema) of the lower layer of skin and tissue just under the skin or mucous membranes. The swelling may occur in the face, tongue, larynx, abdomen, or arms and legs. Often it is associated with hives, which ar ...

Common: #

Joint A joint or articulation (or articular surface) is the connection made between bones, ossicles, or other hard structures in the body which link an animal's skeletal system into a functional whole.Saladin, Ken. Anatomy & Physiology. 7th ed. McGraw ...

aches (arthralgia) or

muscle Skeletal muscles (commonly referred to as muscles) are Organ (biology), organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other ...

aches (myalgia) #

Nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

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 ...

(C. diff associated) or vomiting #

Rash A rash is a change of the human skin which affects its color, appearance, or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cr ...

itching Itch (also known as pruritus) is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to be classified as any one type of sensory experience. Itch has many similarities to pain, and while both are unpleasant ...

Headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a resul ...

Hyperbilirubinemia Bilirubin (BR) (Latin for "red bile") is a red-orange compound that occurs in the normal catabolic pathway that breaks down heme in vertebrates. This catabolism is a necessary process in the body's clearance of waste products that arise from the ...

Anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, ...

# Thrombophlebitis

Drug interactions

The drug inhibits P450 and enhances the effects of terfenadine,

astemizole Astemizole (marketed under the brand name Hismanal, developmental code R43512) was a second-generation antihistamine drug that has a long duration of action. Astemizole was discovered by Janssen Pharmaceutica in 1977. It was withdrawn from the ma ...

, indinavir,

midazolam Midazolam, sold under the brand name Versed among others, is a benzodiazepine medication used for anesthesia and procedural sedation, and to treat severe agitation. It works by inducing sleepiness, decreasing anxiety, and causing a loss of ...

, calcium channel blockers,

warfarin Warfarin, sold under the brand name Coumadin among others, is a medication that is used as an anticoagulant (blood thinner). It is commonly used to prevent blood clots such as deep vein thrombosis and pulmonary embolism, and to prevent ...

cisapride Cisapride is a gastroprokinetic agent, a drug that increases motility in the upper gastrointestinal tract. It acts directly as a serotonin 5-HT4 receptor agonist and indirectly as a parasympathomimetic. Stimulation of the serotonin receptors i ...

and

ciclosporin Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is a natural product. It is taken orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's diseas ...

Administration

Mechanism of action

Pharmacokinetics

Side effects

Drug interactions

References

Further reading