Omadacycline: Development of a novel aminomethylcycline antibiotic for treating drug-resistant bacterial infections

Future Microbiology

Volumn 11, Issue 11, 2016, Pages 1421-1434

  Villano, Stephen ^a   Steenbergen, Judith ^a   Loh, Evan ^a  

^a Transcept Pharmaceuticals Inc   (United States)

Author keywords

aminomethylcycline; bacterial infection; omadacycline; tetracyclines

Indexed keywords

ALANINE AMINOTRANSFERASE; ASPARTATE AMINOTRANSFERASE; CREATINE KINASE; OMADACYCLINE; TETRACYCLINE DERIVATIVE;

AGE; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANTIBIOTIC RESISTANCE; ANTIBIOTIC THERAPY; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; BACTERIAL INFECTION; BACTERIAL PNEUMONIA; BACTERIAL SKIN DISEASE; CARDIOVASCULAR EFFECT; CONSTIPATION; CREATINE KINASE BLOOD LEVEL; DECREASED APPETITE; DIARRHEA; DIZZINESS; DRUG ABSORPTION; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG EXCRETION; DRUG METABOLISM; DRUG SAFETY; DRUG TOLERABILITY; DYSGEUSIA; FATIGUE; FOOD; GENDER; HEADACHE; HUMAN; INSOMNIA; LIVER DYSFUNCTION; METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS; MICROBIOLOGY; NAUSEA; NONHUMAN; PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); RASH; REVIEW; SIDE EFFECT; STREPTOCOCCUS PNEUMONIAE; VANCOMYCIN RESISTANT ENTEROCOCCUS; VOMITING; BACTERIAL INFECTIONS; BACTERIUM; CHEMISTRY; CHLAMYDIA; COMMUNITY-ACQUIRED INFECTIONS; DRUG ADMINISTRATION; DRUG EFFECTS; GRAM NEGATIVE AEROBIC RODS AND COCCI; GRAM POSITIVE BACTERIUM; LEGIONELLA; MICROBIAL SENSITIVITY TEST; MULTIDRUG RESISTANCE; SKIN; SKIN DISEASES, BACTERIAL;

BACTERIA; BACTERIAL INFECTIONS; CHLAMYDIA; COMMUNITY-ACQUIRED INFECTIONS; DRUG ADMINISTRATION SCHEDULE; DRUG RESISTANCE, MULTIPLE, BACTERIAL; GRAM-NEGATIVE AEROBIC BACTERIA; GRAM-POSITIVE BACTERIA; LEGIONELLA; METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS; MICROBIAL SENSITIVITY TESTS; SKIN; SKIN DISEASES, BACTERIAL; STREPTOCOCCUS PNEUMONIAE; TETRACYCLINES; VANCOMYCIN-RESISTANT ENTEROCOCCI;

EID: 84994184713     PISSN: 17460913     EISSN: 17460921     Source Type: Journal    
DOI: 10.2217/fmb-2016-0100     Document Type: Review

References (36)

1. Cook M, Molto E, Anderson C. Fluorochrome labeling in Roman period skeletons from Dakhleh Oasis, Egypt. Am. J. Phys. Anthropol. 80(2), 137-143 (1989).
2. Zakeri B, Wright GD. Chemical biology of tetracycline antibiotics. Biochem. Cell Biol. 86(2), 124-136 (2008).
3. Chopra I, Roberts M. Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiol. Mol. Biol. Rev. 65(2), 232-260 (2001).
4. Tasina E, Haidich AB, Kokkali S, Arvanitidou M. Efficacy and safety of tigecycline for the treatment of infectious diseases: a meta-analysis. Lancet Infect. Dis. 11(11), 834-844 (2011).
5. Honeyman L, Ismail M, Nelson M et al. Structure-activity relationship of the aminomethylcyclines and the discovery of omadacycline. Antimicrob. Agents Chemother. 59(11), 7044-7053 (2015).
6. Draper MP, Weir S, Macone A et al. Mechanism of action of the novel aminomethylcycline antibiotic omadacycline. Antimicrob. Agents Chemother. 58(3), 1279-1283 (2014).
7. Macone AB, Caruso BK, Leahy RG et al. In vitro and in vivo antibacterial activities of omadacycline, a novel aminomethylcycline. Antimicrob. Agents Chemother. 58(2), 1127-1135 (2014).
8. Weir S, Macone A, Donatelli J et al. The mechanism of action of BAY 73-6944/PTK 0796. Presented at: 43rd Interscience Congress on Antimicrobial Agents and Chemotherapy. Chicago, IL, USA, 14-17 September 2003.
9. Bhatia B, Bowser T, Chen J et al. PTK 0796 and other novel tetracycline derivatives exhibiting potent in vitro and in vivo activities against antibiotic resistant Gram-positive bacteria. Presented at: 43rd Interscience Congress on Antimicrobial Agents and Chemotherapy. Chicago, IL, USA, 14-17 September 2003.
10. Biedenbach DJ, Mendes RE, Sader HS, Jones RN. In vitro evaluation of PTK796 activity tested against Staphylococcus aureus including hospital-and community-associated MRSA strains from the USA and Europe. Presented at: 50th Interscience Congress on Antimicrobial Agents and Chemotherapy. Boston, MA, USA, 12-15 September 2010.
11. Flamm RK, Rhomberg PR, Huband MD, Farrell DJ. Activity of omadacycline tested against Staphylococcus aureus from a global surveillance program (2014). Presented at: 55th Interscience Congress on Antimicrobial Agents and Chemotherapy. San Diego, CA, USA, 17-21 September 2015.
12. Flamm RK, Rhomberg PR, Huband MD, Farrell DJ. Activity of omadacycline tested against Streptococcus pneumoniae from a global surveillance program (2014). Presented at: 55th Interscience Congress on Antimicrobial Agents and Chemotherapy. San Diego, CA, USA, 17-21 September 2015.
13. Flamm RK, Rhomberg PR, Huband MD, Farrell DJ. Activity of omadacycline tested against Enterobacteriaceae causing urinary tract infections from a global surveillance program (2014). Presented at: 55th Interscience Congress on Antimicrobial Agents and Chemotherapy. San Diego, CA, USA, 17-21 September 2015.
14. Traczewski MM, Brown SB. BAY 73-6944/PTK 0796: in vitro potency and spectrum of activity compared with ten other antimicrobial compounds. Presented at: 43rd Interscience Congress on Antimicrobial Agents and Chemotherapy. Chicago, IL, USA, 14-17 September 2003.
15. DuBois J, Dubois M, Martel JF, Tanaka SK. In vitro activity of omadacycline against Legionella pneumophila. Presented at: 55th Interscience Congress on Antimicrobial Agents and Chemotherapy. San Diego, CA, USA, 17-21 September 2015.
16. Hanna I, Sun H, Zhu B et al. Metabolic stability of PTK 0796 (omadacycline). Presented at: 22nd European Congress of Clinical Microbiology and Infectious Diseases. London, UK, 31 March-2 April 2012.
17. Hanna I, Sun H, Alexander N et al. Lack of interaction of PTK 0796 (omadacycline) with human transporter. Presented at: 22nd European Congress of Clinical Microbiology and Infectious Diseases. London, UK, 31 March-2 April 2012.
18. Tanaka SK, Villano S. In vitro and in vivo assessment of cardiovascular effects with omadacycline. Antimicrob. Agents Chemther. doi:10.1128/AAC.00320-16 (2016) (Epub ahead of print).
19. Tanaka SK, Villano S, Tzanis E. Single and multiple dose pharmacokinetics and tolerability of intravenous omadacycline in healthy volunteers. Presented at: 26th European Congress of Clinical Microbiology and Infectious Diseases. Amsterdam, The Netherlands, 9-12 April 2016.
20. Sun H, Ting L, Flarakos J et al. Pharmacokinetics of [14C]-labelled omadacycline (PTK 0796) in healthy male subjects. Presented at: 52nd Interscience Congress on Antimicrobial Agents and Chemotherapy. San Francisco, CA, USA, 9-12 September 2012.
21. Villano S, Tzanis E, Tanaka SK. In vitro protein binding with omadacycline, a first in class aminomethylcycline antibiotic. Presented at: ASM Microbe 2016. Boston, MA, USA, 16-20 June 2016.
22. Sun H, Maietta R, Machineni S et al. A single-dose study to evaluate the pharmacokinetics, safety, and tolerability of multiple formulations of PTK 0796 in healthy subjects. Presented at: 21st European Congress of Clinical Microbiology and Infectious Diseases. Milan, Italy, 7-10 May 2011.
23. Craig WA, Andes D, Odinecs A. In vivo pharmacodynamics of MK-2764/PTK 0796 against various Gram-positive and Gramnegative bacteria in the thighs of neutropenic and normal mice. Presented at: 46th Interscience Congress on Antimicrobial Agents and Chemotherapy. San Diego, CA, USA, 27-30 September 2006.
24. Tzanis E, Manley A, Villano S, Tanaka SK, Loh E. Effect of food on the bioavailability of omadacycline in healthy volunteers. Presented at: ASM Microbe 2016. Boston, MA, USA, 16-20 June 2016.
25. Tanaka SK, Tzanis E, Villano S. Effect of age and gender on the pharmacokinetics of the oral and IV omadacycline, a new class of aminomethylcyclines. Presented at: 26th European Congress of Clinical Microbiology and Infectious Diseases. Amsterdam, The Netherlands, 9-12 April 2016.
26. Van Wart SA, Manley A, Bhavnani SM et al. Population pharmacokinetics (PPK) of omadacycline following intravenous (iv) or oral administration to Phase I subjects. Presented at: 26th European Congress of Clinical Microbiology and Infectious Diseases. Amsterdam, The Netherlands, 9-12 April 2016.
27. Villano S, Tanaka SK. Double-blind, randomized study of the effects of a supratherapeutic iv dose of omadacycline on QT/QTc intervals in healthy subjects. Presented at: 26th European Congress of Clinical Microbiology and Infectious Diseases. Amsterdam, The Netherlands, 9-12 April 2016.
28. Ting L, Kovacs SJ, Prestgaard J et al. An open-label study of the pharmacokinetics and safety of single IV and oral doses of omadacycline in subjects with mild, moderate, and severe hepatic impairment. Presented at: 52nd Interscience Congress on Antimicrobial Agents and Chemotherapy. San Francisco, CA, USA, 9-12 September 2012.
29. Noel GJ, Draper MP, Hait H, Tanaka SK, Arbeit RD. A randomized, evaluator-blind, Phase 2 study comparing the safety and efficacy of omadacycline to those of linezolid for treatment of complicated skin and skin structure infections. Antimicrob. Agents Chemother. 56(11), 5650-5654 (2012).
30. Noel GJ, Draper MP, Hait H, Tanaka SK. Safety and efficacy of PTK 0796 (omadacycline) as treatment of complicated skin and soft tissue infection (cSSTI). Presented at: 22nd European Congress of Clinical Microbiology and Infectious Diseases. London, UK, 31 March-2 April 2012.
31. Connors KP, Housman ST, Pope JS et al. Phase I, open-label, safety and pharmacokinetic study to assess bronchopulmonary disposition of intravenous eravacycline in healthy men and women. Antimicrob. Agents Chemother. 58(4), 2113-2118 (2014).
32. Horn PT, Sutcliffe JA, Walpole SM, Leighton A. Pharmacokinetics, safety and tolerability of a novel fluorocycline, TP-434, following multiple dose administration. Presented at: 49th Infectious Diseases Society of American Annual Meeting. Boston, MA, USA, 20-23 October 2011.
33. Leighton A, Zupanets I, Bezugla N, Plamondon L, Macdonald G, Sutcliffe JA. Broad-spectrum fluorocycline TP-434 has oral bioavailability in human. Presented at: 21st European Congress of Clinical Microbiology and Infectious Diseases. Milan, Italy, 7-10 May 2011.
34. Meagher AK, Ambrose PG, Grasela TH, Ellis-Grosse EJ. The pharmacokinetic and pharmacodynamic profile of tigecycline. Clin. Infect. Dis. 41(Suppl. 5), S333-S340 (2005).
35. Passarell J, Ludwig E, Liolios K et al. Exposure-response analyses of tigecycline tolerability in healthy subjects. Diagn. Microbiol. Infect. Dis. 65(2), 123-129 (2009).
36. Rubino CM, Bhavnani SM, Forrest A et al. Pharmacokinetics-pharmacodynamics of tigecycline in patients with communityacquired pneumonia. Antimicrob. Agents Chemother. 56(1), 130-136 (2012).