Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 9/2019

01-09-2019 | Pharmacokinetics | Review Article

Clinical Pharmacokinetics and Pharmacodynamics of Eravacycline

Author: Matthew W. McCarthy

Published in: Clinical Pharmacokinetics | Issue 9/2019

Login to get access

Abstract

On 27 August, 2018, the US Food and Drug Administration approved eravacycline, a fluorocycline antimicrobial agent within the tetracycline class of antibacterial drugs, for the treatment of complicated intra-abdominal infections in patients aged 18 years and older. This decision was based on substantial clinical and pre-clinical data, including rigorous pharmacokinetic and pharmacodynamic work. This paper examines the in-vivo pharmacokinetic/pharmacodynamic work that led to the approval of eravacycline and explores how this important new antibiotic may be used to treat aggressive multidrug-resistant infections in the years ahead.
Literature
1.
Xiao XY, Hunt DK, Zhou J, Clark RB, Dunwoody N, Fyfe C, et al. Fluorocyclines. 1. 7-Fluoro-9-pyrrolidinoacetamido-6-demethyl-6-deoxytetracycline: a potent, broad spectrum antibacterial agent. J Med Chem. 2012;55(2):597–605.CrossRef
2.
Kang Y, Li Q, Mei L, Zhao H, Bai Y, Shen M, et al. Tetracycline resistance genes are more prevalent in wet soils than in dry soils. Ecotoxicol Environ Saf. 2018;156:337–43.CrossRef
3.
Nelson KM, Viswanathan K, Dawadi S, Duckworth BP, Boshoff HI, Barry CE, et al. Synthesis and pharmacokinetic evaluation of siderophore biosynthesis inhibitors for Mycobacterium tuberculosis. J Med Chem. 2015;58(14):5459–75.CrossRef
4.
Abdallah M, Olafisoye O, Cortes C, Urban C, Landman D, Quale J. Activity of eravacycline against Enterobacteriaceae and Acinetobacter baumannii, including multidrug-resistant isolates, from New York City. Antimicrob Agents Chemother. 2015;59(3):1802–5.CrossRef
5.
Sutcliffe JA, O’Brien W, Fyfe C, Grossman TH. Antibacterial activity of eravacycline (TP-434), a novel fluorocycline, against hospital and community pathogens. Antimicrob Agents Chemother. 2013;57(11):5548–58.CrossRef
6.
Grossman TH, Starosta AL, Fyfe C, O’Brien W, Rothstein DM, Mikolajka A, et al. Target- and resistance-based mechanistic studies with TP-434, a novel fluorocycline antibiotic. Antimicrob Agents Chemother. 2012;56(5):2559–64.CrossRef
7.
8.
9.
Thabit AK, Monogue ML, Nicolau DP. Eravacycline pharmacokinetics and challenges in defining humanized exposure in vivo. Antimicrob Agents Chemother. 2016;60(8):5072–5.CrossRef
10.
11.
Connors KP, Housman ST, Pope JS, Russomanno J, Salerno E, Shore E, 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. 2014;58(4):2113–8.CrossRef
12.
Bassetti M, Vena A, Castaldo N, Righi E, Peghin M. New antibiotics for ventilator-associated pneumonia. Curr Opin Infect Dis. 2018;31(2):177–86.CrossRef
13.
Nation RL, Theuretzbacher U, Tsuji BT, International Society of Anti-Infective Pharmacology (ISAP). Concentration-dependent plasma protein binding: expect the unexpected. Eur J Pharm Sci. 2018;122:341–6.CrossRef
14.
15.
Thabit AK, Monogue ML, Newman JV, Nicolau DP. Assessment of in vivo efficacy of eravacycline against Enterobacteriaceae exhibiting various resistance mechanisms: a dose-ranging study and pharmacokinetic/pharmacodynamic analysis. Int J Antimicrob Agents. 2018;51(5):727–32.CrossRef
16.
Daoud Z, Farah J, Sokhn ES, El Kfoury K, Dahdouh E, Masri K, et al. Multidrug-resistant Enterobacteriaceae in Lebanese Hospital wastewater: implication in the one health concept. Microb Drug Resist. 2018;24(2):166–74.CrossRef
17.
Bathoorn E, Tsioutis C, da Silva Voorham JM, Scoulica EV, Ioannidou E, Zhou K, et al. Emergence of pan-resistance in KPC-2 carbapenemase-producing Klebsiella pneumoniae in Crete, Greece: a close call. J Antimicrob Chemother. 2016;71(5):1207–12.CrossRef
18.
Sheng ZK, Li JJ, Sheng GP, Sheng JF, Li LJ. Emergence of Klebsiella pneumoniae carbapenemase-producing Proteus mirabilis in Hangzhou, China. Chin Med J (Engl). 2010;123(18):2568–70.
19.
20.
Roffey SJ, Obach RS, Gedge JI, Smith DA. What is the objective of the mass balance study? A retrospective analysis of data in animal and human excretion studies employing radiolabeled drugs. Drug Metab Rev. 2007;39(1):17–43.CrossRef
21.
Koulenti D, Song A, Ellingboe A, Abdul-Aziz MH, Harris P, Gavey E, et al. Infections by multidrug-resistant Gram-negative bacteria: what’s new in our arsenal and what’s in the pipeline? Int J Antimicrob Agents. 2019;53(3):211–24.CrossRef
22.
Thaden JT, Pogue JM, Kaye KS. Role of newer and re-emerging older agents in the treatment of infections caused by carbapenem-resistant Enterobacteriaceae. Virulence. 2017;8(4):403–16.CrossRef
23.
Zheng JX, Lin ZW, Sun X, Lin WH, Chen Z, Wu Y, et al. Overexpression of OqxAB and MacAB efflux pumps contributes to eravacycline resistance and heteroresistance in clinical isolates of Klebsiella pneumoniae. Emerg Microbes Infect. 2018;7(1):139.PubMedPubMedCentral
24.
Honore PM, Spapen HD. Eravacycline for treatment of complicated intra-abdominal infections: the fire is not ignited! Ann Transl Med. 2017;5(21):425.CrossRef
25.
Solomkin J, Evans D, Slepavicius A, Lee P, Marsh A, Tsai L, et al. Assessing the efficacy and safety of eravacycline vs ertapenem in complicated intra-abdominal infections in the investigating Gram-negative infections treated with eravacycline (IGNITE 1) trial: a randomized clinical trial. JAMA Surg. 2017;152(3):224–32.CrossRef
26.
Bassetti M, Righi E. Eravacycline for the treatment of intra-abdominal infections. Expert Opin Investig Drugs. 2014;23(11):1575–84.CrossRef
27.
28.
Tripathi PC, Gajbhiye SR, Agrawal GN. Clinical and antimicrobial profile of Acinetobacter spp.: an emerging nosocomial superbug. Adv Biomed Res. 2014;3:13.CrossRef
29.
Mohammed N, Savardekar AR, Patra DP, Narayan V, Nanda A. The 21st-century challenge to neurocritical care: the rise of the superbug Acinetobacter baumannii: a meta-analysis of the role of intrathecal or intraventricular antimicrobial therapy in reduction of mortality. Neurosurg Focus. 2017;43(5):E8.CrossRef
30.
Seifert H, Stefanik D, Sutcliffe JA, Higgins PG. In-vitro activity of the novel fluorocycline eravacycline against carbapenem non-susceptible Acinetobacter baumannii. Int J Antimicrob Agents. 2018;51(1):62–4.CrossRef
31.
32.
Zhang F, Bai B, Xu GJ, Lin ZW, Li GQ, Chen Z, et al. Eravacycline activity against clinical S. aureus isolates from China: in vitro activity, MLST profiles and heteroresistance. BMC Microbiol. 2018;18(1):211.CrossRef
33.
Poulakou G, Lagou S, Karageorgopoulos DE, Dimopoulos G. New treatments of multidrug-resistant Gram-negative ventilator-associated pneumonia. Ann Transl Med. 2018;6(21):423.CrossRef
34.
Mancini S, Kieffer N, Poirel L, Nordmann P. Evaluation of the RAPIDEC® CARBA NP and β-CARBA® tests for rapid detection of carbapenemase-producing Enterobacteriaceae. Diagn Microbiol Infect Dis. 2017;88(4):293–7.CrossRef
Metadata
Title
Clinical Pharmacokinetics and Pharmacodynamics of Eravacycline
Author
Matthew W. McCarthy
Publication date
01-09-2019
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 9/2019
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.1007/s40262-019-00767-z

Other articles of this Issue 9/2019

Clinical Pharmacokinetics 9/2019 Go to the issue

Editorial

Calculation of the Coefficient of Variation of Log-Normally Distributed Parameter Values

Original Research Article

Assessment of Drug–Drug Interactions between Taspoglutide, a Glucagon-Like Peptide-1 Agonist, and Drugs Commonly Used in Type 2 Diabetes Mellitus: Results of Five Phase I Trials

Original Research Article

Effect of Oral Semaglutide on the Pharmacokinetics of Lisinopril, Warfarin, Digoxin, and Metformin in Healthy Subjects

Original Research Article

Microdosed Cocktail of Three Oral Factor Xa Inhibitors to Evaluate Drug–Drug Interactions with Potential Perpetrator Drugs

Original Research Article

Pharmacokinetics and Safety of Olaparib in Patients with Advanced Solid Tumours and Renal Impairment

Review Article

Clinical Pharmacokinetics and Pharmacodynamics of Rifampicin in Human Tuberculosis