- Omadacycline: A Novel Oral and Intravenous Aminomethylcycline Antibiotic Agent.
Omadacycline: A Novel Oral and Intravenous Aminomethylcycline Antibiotic Agent.
Drugs. 2020 Jan 22;:
Authors: Zhanel GG, Esquivel J, Zelenitsky S, Lawrence CK, Adam HJ, Golden A, Hink R, Berry L, Schweizer F, Zhanel MA, Bay D, Lagacé-Wiens PRS, Walkty AJ, Lynch JP, Karlowsky JA
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 (Vd) ranging from 190 to 204 L, a terminal elimination half-life (t½) 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 (Cmax) of 0.5-0.6 mg/L and an area under the plasma concentration-time curve from 0 to infinity (AUC0-∞) of 9.6-11.9 mg h/L. The free plasma area under concentration-time curve divided by the minimum inhibitory concentration (i.e., fAUC24h/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.
PMID: 31970713 [PubMed - as supplied by publisher]
- Unlikely Bedfellows: The Partnering of Antibiotic Stewardship Programs and the Pharmaceutical Industry.
Unlikely Bedfellows: The Partnering of Antibiotic Stewardship Programs and the Pharmaceutical Industry.
Clin Infect Dis. 2020 Jan 23;:
Authors: Tamma PD, Cosgrove SE
PMID: 31970391 [PubMed - as supplied by publisher]
- The role of pharmaceutical companies in antimicrobial stewardship: a case study.
The role of pharmaceutical companies in antimicrobial stewardship: a case study.
Clin Infect Dis. 2020 Jan 23;:
Authors: Hermsen ED, Sibbel RL, Holland S
Rising levels of antimicrobial resistance pose serious dangers to patients, population health, food security, and economic stability worldwide. In response to this threat, the United Nations and the World Health Organization have called for multisectoral, multidisciplinary action, recognizing that human, animal, and environmental health are interdependent. While the pharmaceutical industry clearly has a leading role in developing novel antimicrobials and vaccines, it is also active in many areas supporting antimicrobial stewardship. This article describes why pharmaceutical companies invest in antimicrobial stewardship, outlines why they are well suited to help address this issue, and provides examples of how the pharmaceutical industry can support the responsible use of antimicrobials. Merck & Co., Inc. (Kenilworth, NJ, USA), a large, globally-operating pharmaceutical company that develops and markets both human and veterinary antimicrobials and vaccines is used as a case-study for illustrating industry involvement in antimicrobial stewardship efforts.
PMID: 31970384 [PubMed - as supplied by publisher]
- Use of rapid diagnostics to manage pediatric bloodstream infections? You bet your ASP!
Use of rapid diagnostics to manage pediatric bloodstream infections? You bet your ASP!
J Clin Microbiol. 2020 Jan 22;:
Authors: Gonzalez MD, Yarbrough ML
Rapid diagnostic testing (RDT) can facilitate earlier optimization of treatment of bloodstream infections, particularly in conjunction with an effective antimicrobial stewardship program (ASP). However, effective implementation and workflow of RDTs is still a matter of debate, particularly in a pediatric setting. In this issue of the Journal of Clinical Microbiology, L.J. Juttukonda et al. (J Clin Microbiol 57:e01400-19, https://doi.org/10.1128/JCM.01400-19) investigate the impact of a multiplex, molecular RDT on changes to antimicrobial therapy in an academic children's hospital. These data reveal several factors that clinical laboratories should consider prior to implementation of RDTs for positive blood cultures.
PMID: 31969424 [PubMed - as supplied by publisher]