Oritavancin, sold under the brand name Orbactiv among others, is a

semisynthetic 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 ...

glycopeptide antibiotic Glycopeptide antibiotics are a class of drugs of microbial origin that are composed of glycosylated cyclic or polycyclic nonribosomal peptides. Significant glycopeptide antibiotics include the anti-infective antibiotics vancomycin, teicoplani ...

medication for the treatment of serious Gram-positive bacterial infections. Its chemical structure as a

lipoglycopeptide Lipoglycopeptides are a class of antibiotic that have lipophilic side-chains linked to glycopeptides. The class includes oritavancin, telavancin and dalbavancin. In September 2009 the US Food and Drug Administration (FDA) approved telavancin (Vib ...

is similar to

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 infections, ...

. The U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(FDA) and the European Medicines Agency (EMA) have approved oritavancin for treatment of acute bacterial skin and skin structure infections.

''In vitro'' activity

Oritavancin shares certain properties with other members of the glycopeptide class of antibiotics, which includes

, the current standard of care for serious Gram-positive infections in the United States and Europe. It possesses potent and rapid bactericidal activity ''in vitro'' against a broad spectrum of both resistant and susceptible Gram-positive bacteria, including '' Staphylococcus aureus'',

MRSA Methicillin-resistant ''Staphylococcus aureus'' (MRSA) is a group of Gram-positive bacteria that are genetically distinct from other strains of ''Staphylococcus aureus''. MRSA is responsible for several difficult-to-treat infections in humans. ...

enterococci ''Enterococcus'' is a large genus of lactic acid bacteria of the phylum Bacillota. Enterococci are gram-positive cocci that often occur in pairs (diplococci) or short chains, and are difficult to distinguish from streptococci on physical charac ...

, and streptococci. Oritavancin was more active than either

metronidazole Metronidazole, sold under the brand name Flagyl among others, is an antibiotic and antiprotozoal medication. It is used either alone or with other antibiotics to treat pelvic inflammatory disease, endocarditis, and bacterial vaginosis. It i ...

or vancomycin against strains of '' Clostridium difficile'' tested. Oritavancin has potential use as a therapy for exposure to '' Bacillus anthracis'', the Gram-positive bacterium that causes anthrax, having demonstrated efficacy in a mouse model both before and after exposure to the bacterium. oritavancin demonstrates in vitro activity against both the planktonic and biofilmstates of staphylococci associated with Prosthetic joint infection (PJI), albeit with increased minimum biofilm bactericidal concentration (MBBC) compared to

Minimum inhibitory concentration In microbiology, the minimum inhibitory concentration (MIC) is the lowest concentration of a chemical, usually a drug, which prevents visible growth of a bacterium or bacteria. MIC depends on the microorganism, the affected human being (in vivo only ...

s (MIC) values. Moreever oritavancin has demonstrated activity against in vitro to vancomycin-susceptible enterococci (VSE) and vancomycin-resistant enterococci (VRE) in both planktonic and biofilm states.

Mechanism

The 4'-chloro

biphenyl Biphenyl (also known as diphenyl, phenylbenzene, 1,1′-biphenyl, lemonene or BP) is an organic compound that forms colorless crystals. Particularly in older literature, compounds containing the functional group consisting of biphenyl less one ...

methyl group disrupts the cell membrane of Gram-positive bacteria. It also acts by inhibition of transglycosylation and inhibition of transpeptidation.

Synergism

Several antibiotics have been tested as partner drugs of oritavancin. Among these "companions" drugs, fosfomycin displayed (''in vitro'' and ''in vivo'') synergistic activity when administered together with oritavancin against VRE strains (both ''vanA'' and ''vanB'').

Spectrum of Activity

Oritavancin is active against gram-positive aerobic bacteria such as enterococci, staphylococci, streptococci, and anaerobic bacteria such as '' Clostridium difficile'' , ''

Clostridium perfringens ''Clostridium perfringens'' (formerly known as ''C. welchii'', or ''Bacillus welchii'') is a Gram-positive, rod-shaped, anaerobic, spore-forming pathogenic bacterium of the genus ''Clostridium''. ''C. perfringens'' is ever-present in nature an ...

'' , '' Peptostreptococcus spp.'' , and '' Propionibacterium acnes.'' Oritavancin's spectrum of activity shows similarities to vancomycin, but with lower minimum inhibitory concentrations (MIC).

Clinical trials

In 2003, results were presented from two pivotal phase-III clinical trials testing the efficacy of daily intravenous oritavancin for the treatment of acute bacterial skin and skin-structure infections (ABSSSI) caused by Gram-positive bacteria. The primary endpoints of both studies were met, with oritavancin achieving efficacy with fewer days of therapy than the comparator agents vancomycin followed by

cephalexin Cefalexin, also spelled cephalexin, is an antibiotic that can treat a number of bacterial infections. It kills gram-positive and some gram-negative bacteria by disrupting the growth of the bacterial cell wall. Cefalexin is a beta-lactam antibi ...

. Oritavancin showed a statistically significant improved safety profile with a 19% relative reduction in the overall incidence of adverse events versus vancomycin/cephalexin in the second and larger pivotal trial.

Osteomyelitis Osteomyelitis (OM) is an infection of bone. Symptoms may include pain in a specific bone with overlying redness, fever, and weakness. The long bones of the arms and legs are most commonly involved in children e.g. the femur and humerus, while the ...

remains a formidable foe in an era of increasing incidence of

Methicillin-resistant Staphylococcus aureus Methicillin-resistant ''Staphylococcus aureus'' (MRSA) is a group of Gram-positive bacteria that are genetically distinct from other strains of '' Staphylococcus aureus''. MRSA is responsible for several difficult-to-treat infections in human ...

(MRSA) with limited guidance for treatment optimization. The success observed in many patients suggests multi-dose oritavancin may prove advantageous for chronic osteomyelitis but further research is needed to define the optimal dose and frequency of oritavancin for the treatment of chronic osteomyelitis.

History

Originally discovered and developed by

Eli Lilly Eli Lilly (July 8, 1838 – June 6, 1898) was an American soldier, pharmacist, chemist, and businessman who founded the Eli Lilly and Company pharmaceutical corporation. Lilly enlisted in the Union Army during the American Civil War and ...

, oritavancin was acquired by InterMune in 2001 and then by Targanta Therapeutics in late 2005. In December 2008, the U.S.

(FDA) declined to approve oritavancin without additional studies, and an EU application was withdrawn. In 2009, The Medicines Company acquired the development rights, completed clinical trials and submitted a new drug application to the FDA in February 2014. On August 6, 2014, the United States FDA approved oritavancin to treat

skin infections Skin and skin structure infections (SSSIs), also referred to as skin and soft tissue infections (SSTIs), or acute bacterial skin and skin structure infections (ABSSSIs), are infections of skin and associated soft tissues (such as loose connective ti ...

. A marketing authorisation valid throughout the

European Union The European Union (EU) is a supranational political and economic union of member states that are located primarily in Europe. The union has a total area of and an estimated total population of about 447million. The EU has often been de ...

was granted on 19 March 2015, for the treatment of acute bacterial skin and skin structure infections in adults.

References

External links

* {{Portal bar , Medicine CYP3A4 inducers Eli Lilly and Company brands Glycopeptide antibiotics