Oritavancin

Oritavancin
Names
Pronunciation/oʊˌrɪtəˈvænsɪn/
oh-RIT-ə-VAN-sin
Trade namesOrbactiv, Kimyrsa, Tenkasi, others
Other namesLY333328
IUPAC name
  • (4R)-22-O-(3-Amino-2,3,6-trideoxy-3-C-methyl-α-L-arabinohexopyranosyl)-N3-(p-(p-chlorophenyl)benzyl)vancomycin
Clinical data
Drug classAntibiotic (lipoglycopeptide)[1]
Main usesSkin and skin structure infections[1]
Side effectsDiarrhea, nausea, dizziness, headache, itchiness, fever, liver problems[1]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Routes of
use		Intravenous
Typical dose1,200 mg[2]
External links
AHFS/Drugs.comMonograph
MedlinePlusa614042
Legal
License data
Legal status
Chemical and physical data
FormulaC86H97Cl3N10O26
Molar mass1793.12 g·mol−1
3D model (JSmol)
SMILES
  • C[C@H]1[C@@H]([C@@](C[C@@H](O1)O[C@H]2[C@H]3C(=O)N[C@H](C4=C(C(=CC(=C4)O)O)C5=C(C=CC(=C5)[C@H](C(=O)N3)NC(=O)[C@H]6C7=CC(=C(C(=C7)OC8=C(C=C(C=C8)[C@H]([C@H](C(=O)N[C@H](C(=O)N6)CC(=O)N)NC(=O)[C@@H](CC(C)C)NC)O)Cl)O[C@H]9[C@@H]([C@H]([C@@H]([C@H](O9)CO)O)O)O[C@H]1C[C@]([C@H]([C@@H](O1)C)O)(C)NCC1=CC=C(C=C1)C1=CC=C(C=C1)Cl)OC1=C(C=C2C=C1)Cl)O)C(=O)O)(C)N)O
InChI
  • InChI=1S/C86H97Cl3N10O26/c1-35(2)22-51(92-7)77(110)98-67-69(105)42-15-20-55(49(88)24-42)120-57-26-44-27-58(73(57)125-84-74(71(107)70(106)59(34-100)122-84)124-62-32-86(6,76(109)37(4)119-62)93-33-38-8-10-39(11-9-38)40-12-17-45(87)18-13-40)121-56-21-16-43(25-50(56)89)72(123-61-31-85(5,91)75(108)36(3)118-61)68-82(115)97-66(83(116)117)48-28-46(101)29-54(103)63(48)47-23-41(14-19-53(47)102)64(79(112)99-68)96-80(113)65(44)95-78(111)52(30-60(90)104)94-81(67)114/h8-21,23-29,35-37,51-52,59,61-62,64-72,74-76,84,92-93,100-103,105-109H,22,30-34,91H2,1-7H3,(H2,90,104)(H,94,114)(H,95,111)(H,96,113)(H,97,115)(H,98,110)(H,99,112)(H,116,117)/t36-,37-,51+,52-,59+,61-,62-,64+,65+,66+,67+,68-,69+,70+,71-,72+,74+,75-,76-,84-,85-,86-/m0/s1 ☒N
  • Key:VHFGEBVPHAGQPI-MYYQHNLBSA-N ☒N

Oritavancin, sold under the brand name Orbactiv among others, is an antibiotic used to treat skin and skin structure infections such as cellulitis and skin abscesses.[1][2] It is also effective against MRSA.[1] It is given by injection into a vein.[1]

Common side effects include diarrhea, nausea, dizziness, headache, itchiness, fever, and liver problems.[1] Safety in pregnancy is unclear.[5] It is a glycopeptide specifically a lipoglycopeptide and is similar to vancomycin.[1] It works by stopping bacteria from making their cell wall.[2]

Oritavancin was approved for medical use in the United States in 2014 and Europe in 2015.[1][2] In the United States a course of treatments costs about 3,000 USD.[6] It; however, is not commercially available in the United Kingdom or Europe as of 2021.[7]

Medical uses

It is used for skin and skin structure infections such as cellulitis and skin abscesses.[1][2] It is also effective against MRSA.[1]

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 , Peptostreptococcus spp. , and Propionibacterium acnes.[8][9] Oritavancin’s spectrum of activity shows similarities to vancomycin, but with lower minimum inhibitory concentrations (MIC).[10]

Dosage

It is generally given as a single dose of 1,200 mg.[2]

Mechanism

The 4'-chlorobiphenylmethyl group disrupts the cell membrane of Gram-positive bacteria.[11] It also acts by inhibition of transglycosylation and inhibition of transpeptidation.[12]

History

Originally discovered and developed by Eli Lilly, oritavancin was acquired by InterMune in 2001 and then by Targanta Therapeutics in late 2005.[13] In December 2008, the U.S. Food and Drug Administration (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.[14] On August 6, 2014, the United States FDA approved oritavancin to treat skin infections.[15]

A marketing authorisation valid throughout the European Union was granted on 19 March 2015, for the treatment of acute bacterial skin and skin structure infections in adults.[16]

Research

Oritavancin shares certain properties with other members of the glycopeptide class of antibiotics, which includes vancomycin, the current standard of care for serious Gram-positive infections in the United States and Europe.[17] 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, enterococci, and streptococci.[18] Oritavancin was more active than either metronidazole or vancomycin against strains of Clostridium difficile tested.[19]

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.[20]

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 concentrations (MIC) values.[21] Moreever oritavancin has demonstrated activity against in vitro to vancomycin-susceptible enterococci (VSE) and vancomycin-resistant enterococci (VRE) in both planktonic and biofilm states.[22]

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. 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.[23]

Osteomyelitis remains a formidable foe in an era of increasing incidence of Methicillin-resistant Staphylococcus aureus (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.[24]

References

  1. 1 2 3 4 5 6 7 8 9 10 11 "Oritavancin Monograph for Professionals". Drugs.com. Archived from the original on 28 January 2021. Retrieved 8 November 2021.
  2. 1 2 3 4 5 6 7 "Orbactiv EPAR". Archived from the original on 2020-12-28. Retrieved 2021-09-05.
  3. ↑ "Orbactiv- oritavancin injection, powder, lyophilized, for solution". DailyMed. Archived from the original on 24 March 2021. Retrieved 18 December 2020.
  4. ↑ "Kimyrsa- oritavancin diphosphate injection, powder, lyophilized, for solution". DailyMed. Archived from the original on 19 April 2021. Retrieved 31 March 2021.
  5. ↑ "Oritavancin Use During Pregnancy". Drugs.com. Archived from the original on 29 November 2020. Retrieved 8 November 2021.
  6. ↑ "Orbactiv Prices, Coupons & Savings Tips - GoodRx". GoodRx. Archived from the original on 13 June 2016. Retrieved 8 November 2021.
  7. ↑ "Oritavancin". SPS - Specialist Pharmacy Service. 28 September 2015. Archived from the original on 9 November 2021. Retrieved 8 November 2021.
  8. ↑ Mendes RE, Woosley LN, Farrell DJ, Sader HS, Jones RN (March 2012). "Oritavancin activity against vancomycin-susceptible and vancomycin-resistant Enterococci with molecularly characterized glycopeptide resistance genes recovered from bacteremic patients, 2009-2010". Antimicrobial Agents and Chemotherapy. 56 (3): 1639–42. doi:10.1128/AAC.06067-11. PMC 3294904. PMID 22183169.
  9. ↑ Mendes RE, Sader HS, Flamm RK, Jones RN (June 2014). "Activity of oritavancin tested against uncommonly isolated Gram-positive pathogens responsible for documented infections in hospitals worldwide". The Journal of Antimicrobial Chemotherapy. 69 (6): 1579–81. doi:10.1093/jac/dku016. PMID 24505091.
  10. ↑ Arhin FF, Draghi DC, Pillar CM, Parr TR, Moeck G, Sahm DF (November 2009). "Comparative in vitro activity profile of oritavancin against recent gram-positive clinical isolates". Antimicrobial Agents and Chemotherapy. 53 (11): 4762–71. doi:10.1128/AAC.00952-09. PMC 2772347. PMID 19738026.
  11. ↑ Belley A, McKay GA, Arhin FF, Sarmiento I, Beaulieu S, Fadhil I, et al. (December 2010). "Oritavancin disrupts membrane integrity of Staphylococcus aureus and vancomycin-resistant enterococci to effect rapid bacterial killing". Antimicrobial Agents and Chemotherapy. 54 (12): 5369–71. doi:10.1128/AAC.00760-10. PMC 2981232. PMID 20876372.
  12. ↑ Zhanel GG, Schweizer F, Karlowsky JA (April 2012). "Oritavancin: mechanism of action". Clinical Infectious Diseases. 54 Suppl 3: S214-9. doi:10.1093/cid/cir920. PMID 22431851.
  13. ↑ Tomoko Okudaira (2014-05-09). "The Daily Biopharmaceutical News Source". BioWorld. Archived from the original on 2021-10-25. Retrieved 2014-06-06.
  14. ↑ "Biotechs pick up slack in antibiotics development". 17 May 2011. Archived from the original on 2016-03-04. Retrieved 2021-09-05.
  15. ↑ "FDA approves Orbactiv to treat skin infections" (Press release). U.S. Food and Drug Administration (FDA). 6 August 2014. Archived from the original on 8 August 2014.
  16. ↑ "EPAR summary: Orbactiv" (PDF). European Medicines Agency. Archived (PDF) from the original on 2018-06-19. Retrieved 2021-09-05.
  17. ↑ Scheinfeld N (January 2007). "A comparison of available and investigational antibiotics for complicated skin infections and treatment-resistant Staphylococcus aureus and enterococcus". Journal of Drugs in Dermatology. 6 (1): 97–103. PMID 17373167.
  18. ↑ 2007 ICAAC Posters: E-1612 “In Vitro Activity Profile of Oritavancin against a Broad Spectrum of Aerobic and Anaerobic Bacterial Pathogens”/E -1613 “In Vitro Activity Profile of Oritavancin (ORI) Against Organisms Demonstrating Key Resistance Profiles to Other Antimicrobial Agents”/E-1614 “In vitro Time Kill Studies of Oritavancin against Drug-resistant Isolates of Staphylococcus aureus and Enterococci”/E-1615 “Anti-Enterococcal Activity Profile of Oritavancin, a Potent Lipoglycopeptide under Development for Use Against Gram-Positive Infections”/E-1616 “Anti-Streptococcal Activity Profile of Oritavancin, a Potent Lipoglycopeptide under Development for Use Against Gram-Positive Infections”/E-1617 “In Vitro Activity Profile of Oritavancin (ORI) Against Resistant Staphylococcal Populations From a Recent Surveillance Initiative”/E-1620 “Pharmacokinetic Concentrations of Oritavancin Kill Stationary-Phase and Biofilm Staphylococcus aureus In Vitro.” / Targanta Press Release September 19, 2007 Archived July 13, 2011, at the Wayback Machine
  19. ↑ ICAAC 2007 Posters: “In Vitro Susceptibility of Genotypically Distinct Clostridium difficile Strains to Oritavancin” and “Activity of Metronidazole, Vancomycin and Oritavancin Against Epidemic Clostridium difficile Spores” / Targanta Press Release September 19, 2007 Archived July 13, 2011, at the Wayback Machine
  20. ↑ ASM 2007 Poster: “Efficacy of Oritavancin in a Murine Model of Bacillus anthracis Spore Inhalation Anthrax” / Targanta Press Release May 24, 2007 Archived July 13, 2011, at the Wayback Machine
  21. ↑ Yan, Qun, Melissa J. Karau, and Robin Patel. “In Vitro Activity of Oritavancin against Biofilms of Staphylococci Isolated from Prosthetic Joint Infection.” Diagnostic Microbiology and Infectious Disease 92, no. 2 (October 2018): 155–57. https://doi.org/10.1016/j.diagmicrobio.2018.05.010 Archived 2021-10-25 at the Wayback Machine.
  22. ↑ Yan, Qun, Melissa J. Karau, and Robin Patel. “In Vitro Activity of Oritavancin against Planktonic and Biofilm States of Vancomycin-Susceptible and Vancomycin-Resistant Enterococci.” Diagnostic Microbiology and Infectious Disease 91, no. 4 (August 2018): 348–50. https://doi.org/10.1016/j.diagmicrobio.2018.03.008 Archived 2021-10-25 at the Wayback Machine.
  23. ↑ ICAAC 2003 Late-breaker poster: "Phase III Trial Comparing 3–7 days of Oritavancin vs. 10–14 days of Vancomycin/Cephalexin in the Treatment of Patients with Complicated Skin and Skin Structure Infections (cSSSI)" / InterMune Press Release September 15, 2003
  24. ↑ Chastain, Daniel B., and Anthony Davis. “Treatment of Chronic Osteomyelitis with Multidose Oritavancin: A Case Series and Literature Review.” International Journal of Antimicrobial Agents 53, no. 4 (April 2019): 429–34. https://doi.org/10.1016/j.ijantimicag.2018.11.023 Archived 2021-10-25 at the Wayback Machine.
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