| Synonyms | PTK 0796; PTK-0796; PTK0796; Amadacyclin; Omadacycline;(4S,4aS,5aR,12aS)-4,7-bis(Dimethylamino)-9-(((2,2-dimethylpropyl)amino)methyl)- 3,10,12,12a- tetrahydroxy-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2- carboxamide
|
| Reference | 1. Clin Infect Dis. 2019 Aug 1;69(Suppl 1):S6-S15. doi: 10.1093/cid/ciz395.
<br>
Microbiology and Preclinical Review of Omadacycline.
<br>
Karlowsky JA(1), Steenbergen J(2), Zhanel GG(1).
<br>
Author information:<br>
(1)Department of Medical Microbiology and Infectious Diseases, Max Rady College
of Medicine, University of Manitoba, Winnipeg, Canada.
(2)Paratek Pharmaceuticals, Inc., King of Prussia, Pennsylvania.
<br>
Omadacycline is a novel aminomethylcycline antimicrobial and semisynthetic
derivative of tetracycline. In vitro, omadacycline displays potent activity
against gram-positive and many gram-negative bacteria, including
methicillin-resistant Staphylococcus aureus, Streptococcus pneumoniae,
β-hemolytic streptococci, vancomycin-resistant Enterococcus, and
Enterobacteriaceae. Omadacycline is also active against atypical and anaerobic
pathogens, including Legionella pneumophila, Mycoplasma spp., Ureaplasma spp.,
Bacteroides spp., and Clostridioides difficile. This review outlines the
microbiology and preclinical studies of omadacycline, including its mechanism of
action; spectrum of activity; protein binding; activity in the presence of
surfactant, serum, normal, and pH-adjusted urine, or bacterial biofilms;
postantibiotic effect; pharmacodynamic properties; and in vitro and in vivo
efficacy. The results of in vitro and in vivo animal studies support the
observations made in phase III clinical trials and the clinical development of
omadacycline.
<br><br>
2. Ann Pharmacother. 2019 May;53(5):486-500. doi: 10.1177/1060028018818094. Epub
2018 Dec 7.
<br>
Omadacycline: A New Tetracycline Antibiotic.
<br>
Dougherty JA(1), Sucher AJ(2), Chahine EB(1), Shihadeh KC(3).
<br>
Author information:<br>
(1)1 Palm Beach Atlantic University, West Palm Beach, FL, USA.
(2)2 Regis University, Denver, CO, USA.
(3)3 Denver Health Medical Center, Denver, CO, USA.
<br>
OBJECTIVE: To review the chemistry, pharmacology, microbiology,
pharmacokinetics, pharmacodynamics, clinical efficacy, tolerability, dosage, and
administration of omadacycline, a new tetracycline antibiotic.
DATA SOURCES: A literature search through PubMed, Google Scholar, and
clinicaltrials.gov was conducted (2008 to October 2018) using the search terms
omadacycline and PTK-0796. Abstracts presented at recent conferences,
prescribing information and information from the FDA and the manufacturer’s
website were reviewed.
STUDY SELECTION AND DATA EXTRACTION: Preclinical data and published phase 1, 2,
and 3 studies were evaluated.<br>
DATA SYNTHESIS: Omadacycline displays in vitro activity against a wide range of
bacteria. Clinical trials have shown that omadacycline is noninferior to
linezolid for the treatment of acute bacterial skin and skin structure
infections (ABSSSI) and noninferior to moxifloxacin for the treatment of
community-acquired bacterial pneumonia (CABP). A loading dose of 200 mg
intravenously (IV) once or 100 mg IV twice or 450 mg orally once is recommended
followed by a maintenance dose of 100 mg IV or 300 mg orally once daily. No
dosage adjustment is needed in patients with renal or hepatic impairment.
Omadacycline is well tolerated, with nausea being a common adverse effect, but
is associated with food and drug interactions. Relevance to Patient Care and
Clinical Practice: Omadacycline is active against staphylococci, including
methicillin-resistant strains, and streptococci, including
tetracycline-resistant strains, as well as atypical bacteria. Omadacycline
provides clinicians with an additional parenteral and oral option for the
treatment of adults with ABSSSI and CABP.<br>
CONCLUSION: Omadacycline is an alternative treatment option for ABSSSI and CABP.
<br><br>
3. J Antimicrob Chemother. 2019 Oct 1;74(10):2930-2933. doi: 10.1093/jac/dkz267.
<br>
Omadacycline as a promising new agent for the treatment of infections with
Mycobacterium abscessus.
<br>
Bax HI(1)(2), de Vogel CP(2), Mouton JW(2), de Steenwinkel JEM(2).
<br>
Author information:<br>
(1)Department of Internal Medicine, Division of Infectious Diseases, Erasmus
University Medical Centre, Rotterdam, The Netherlands.
(2)Department of Medical Microbiology and Infectious Diseases, Erasmus
University Medical Centre, Rotterdam, The Netherlands.
<br>
BACKGROUND: Despite intensive treatment regimens, the outcome of Mycobacterium
abscessus infections is extremely poor and thus novel treatment regimens are
needed. Although tigecycline seems to be one of the best options currently
available, its long-term use is hampered by severe toxic side effects as well as
the need for intravenous administration and the relatively high concentrations
required for efficacy.<br>
OBJECTIVES: To assess the in vitro activity of omadacycline against M. abscessus
and compare it with the activity of tigecycline.<br>
METHODS: The concentration- and time-dependent killing capacities of
omadacycline and tigecycline against M. abscessus subspecies abscessus were
determined using a time-kill kinetics assay. Time-kill curves as well as
concentration-effect curves were generated.<br>
RESULTS: Time-kill curves showed strong concentration-dependent antimicrobial
activity for both omadacycline and tigecycline. Omadacycline showed inhibition
of mycobacterial growth at 4 mg/L and mycobacterial killing at concentrations
≥16 mg/L. Tigecycline showed mycobacterial killing at concentrations ≥4 mg/L,
achieving elimination at concentrations ≥16 mg/L. The concentration-effect
curves after 7 days of exposure showed stasis, 1 log mycobacterial killing and
2 log mycobacterial killing at 3.3, 4.0 and 4.8 mg/L for omadacycline and 2.2,
2.7 and 3.4 mg/L for tigecycline, respectively.<br>
CONCLUSIONS: The results of this in vitro study on omadacycline activity,
together with its favourable (pharmacokinetic) properties, suggest that
omadacycline is a potential new agent for the treatment of M. abscessus
infections.
<br>
|
