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| DOI | 10.1007/s40265-020-01257-4 |
| Omadacycline: A Novel Oral and Intravenous Aminomethylcycline Antibiotic Agent | |
| Zhanel, George G.1,6; Esquivel, Jenine2; Zelenitsky, Sheryl2; Lawrence, Courtney K.2; Adam, Heather J.1,3; Golden, Alyssa1; Hink, Rachel1; Berry, Liam4; Schweizer, Frank1,4; Zhanel, Michael A.1; Bay, Denice1; Lagace-Wiens, Philippe R. S.1,3; Walkty, Andrew J.1,3; Lynch, Joseph P., III5; Karlowsky, James A.1,3 | |
| 通讯作者 | Zhanel, George G. |
| 来源期刊 | DRUGS
 |
| ISSN | 0012-6667 |
| EISSN | 1179-1950 |
| 出版年 | 2020 |
| 卷号 | 80期号:3页码:285-313 |
| 英文摘要 | Omadacycline is a novel aminomethylcycline antibiotic developed as a once-daily, intravenous and oral treatment for acute bacterial skin and skin structure infection (ABSSSI) and community-acquired bacterial pneumonia (CABP). Omadacycline, a derivative of minocycline, has a chemical structure similar to tigecycline with an alkylaminomethyl group replacing the glycylamido group at the C-9 position of the D-ring of the tetracycline core. Similar to other tetracyclines, omadacycline inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit. Omadacycline possesses broad-spectrum antibacterial activity against Gram-positive and Gram-negative aerobic, anaerobic, and atypical bacteria. Omadacycline remains active against bacterial isolates possessing common tetracycline resistance mechanisms such as efflux pumps (e.g., TetK) and ribosomal protection proteins (e.g., TetM) as well as in the presence of resistance mechanisms to other antibiotic classes. The pharmacokinetics of omadacycline are best described by a linear, three-compartment model following a zero-order intravenous infusion or first-order oral administration with transit compartments to account for delayed absorption. Omadacycline has a volume of distribution (V-d) ranging from 190 to 204 L, a terminal elimination half-life (t(1/2)) of 13.5-17.1 h, total clearance (CLT) of 8.8-10.6 L/h, and protein binding of 21.3% in healthy subjects. Oral bioavailability of omadacycline is estimated to be 34.5%. A single oral dose of 300 mg (bioequivalent to 100 mg IV) of omadacycline administered to fasted subjects achieved a maximum plasma concentration (C-max) of 0.5-0.6 mg/L and an area under the plasma concentration-time curve from 0 to infinity (AUC(0-infinity)) of 9.6-11.9 mg h/L. The free plasma area under concentration-time curve divided by the minimum inhibitory concentration (i.e., fAUC(24h)/MIC), has been established as the pharmacodynamic parameter predictive of omadacycline antibacterial efficacy. Several animal models including neutropenic murine lung infection, thigh infection, and intraperitoneal challenge model have documented the in vivo antibacterial efficacy of omadacycline. A phase II clinical trial on complicated skin and skin structure infection (cSSSI) and three phase III clinical trials on ABSSSI and CABP demonstrated the safety and efficacy of omadacycline. The phase III trials, OASIS-1 (ABSSSI), OASIS-2 (ABSSSI), and OPTIC (CABP), established non-inferiority of omadacycline to linezolid (OASIS-1, OASIS-2) and moxifloxacin (OPTIC), respectively. Omadacycline is currently approved by the FDA for use in treatment of ABSSSI and CABP. Phase II clinical trials involving patients with acute cystitis and acute pyelonephritis are in progress. Mild, transient gastrointestinal events are the predominant adverse effects associated with use of omadacycline. Based on clinical trial data to date, the adverse effect profile of omadacycline is similar to studied comparators, linezolid and moxifloxacin. Unlike tigecycline and eravacycline, omadacycline has an oral formulation that allows for step-down therapy from the intravenous formulation, potentially facilitating earlier hospital discharge, outpatient therapy, and cost savings. Omadacycline has a potential role as part of an antimicrobial stewardship program in the treatment of patients with infections caused by antibiotic-resistant and multidrug-resistant Gram-positive [including methicillin-resistant Staphylococcus aureus (MRSA)] and Gram-negative pathogens. |
| 类型 | Review |
| 语种 | 英语 |
| 国家 | Canada ; USA |
| 收录类别 | SCI-E |
| WOS记录号 | WOS:000508706600001 |
| WOS关键词 | IN-VITRO ACTIVITY ; ACUTE BACTERIAL SKIN ; STREPTOCOCCUS-PNEUMONIAE ; TETRACYCLINE ANTIBIOTICS ; TIGECYCLINE ; GLYCYLCYCLINE ; SAFETY ; PHARMACOKINETICS ; SUSCEPTIBILITY ; ERAVACYCLINE |
| WOS类目 | Pharmacology & Pharmacy ; Toxicology |
| WOS研究方向 | Pharmacology & Pharmacy ; Toxicology |
| EI主题词 | 2020-01-22 |
| 来源机构 | University of California, Los Angeles |
| 资源类型 | 期刊论文 |
| 条目标识符 | http://119.78.100.177/qdio/handle/2XILL650/312581 |
| 作者单位 | 1.Univ Manitoba, Dept Med Microbiol & Infect Dis, Max Rady Coll Med, Rady Fac Hlth Sci, Winnipeg, MB, Canada; 2.Univ Manitoba, Coll Pharm, Rady Fac Hlth Sci, Winnipeg, MB, Canada; 3.Shared Hlth, Diagnost Serv, Winnipeg, MB, Canada; 4.Univ Manitoba, Dept Chem, Fac Sci, Winnipeg, MB, Canada; 5.Univ Calif Los Angeles, David Geffen Sch Med, Div Pulm Crit Care Allergy & Clin Immunol, Los Angeles, CA 90095 USA; 6.Hlth Sci Ctr, Clin Microbiol, MS673-820 Sherbrook St, Winnipeg, MB R3A 1R9, Canada |
| 推荐引用方式 GB/T 7714 | Zhanel, George G.,Esquivel, Jenine,Zelenitsky, Sheryl,et al. Omadacycline: A Novel Oral and Intravenous Aminomethylcycline Antibiotic Agent[J]. University of California, Los Angeles,2020,80(3):285-313. |
| APA | Zhanel, George G..,Esquivel, Jenine.,Zelenitsky, Sheryl.,Lawrence, Courtney K..,Adam, Heather J..,...&Karlowsky, James A..(2020).Omadacycline: A Novel Oral and Intravenous Aminomethylcycline Antibiotic Agent.DRUGS,80(3),285-313. |
| MLA | Zhanel, George G.,et al."Omadacycline: A Novel Oral and Intravenous Aminomethylcycline Antibiotic Agent".DRUGS 80.3(2020):285-313. |
| 条目包含的文件 | 条目无相关文件。 | |||||
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