Eravacycline is an investigational, synthetic fluorocycline
antibacterial agent that is structurally similar to
tigecycline with two modifications to the D-ring of its
tetracycline core: a
fluorine atom replaces the
dimethylamine moiety at C-7 and a pyrrolidinoacetamido group replaces the 2-tertiary-butyl glycylamido at C-9. Like other
tetracyclines,
eravacycline inhibits
bacterial protein synthesis through binding to the 30S ribosomal subunit.
Eravacycline demonstrates broad-spectrum antimicrobial activity against Gram-positive, Gram-negative, and anaerobic bacteria with the exception of Pseudomonas aeruginosa.
Eravacycline is two- to fourfold more potent than
tigecycline versus Gram-positive cocci and two- to eightfold more potent than
tigecycline versus Gram-negative bacilli. Intravenous
eravacycline demonstrates linear pharmacokinetics that have been described by a four-compartment model. Oral bioavailability of
eravacycline is estimated at 28 % (range 26-32 %) and a single oral dose of 200 mg achieves a maximum plasma concentration (C max) and area under the plasma concentration-time curve from 0 to infinity (AUC0-∞) of 0.23 ± 0.04 mg/L and 3.34 ± 1.11 mg·h/L, respectively. A population pharmacokinetic study of intravenous (IV)
eravacycline demonstrated a mean steady-state volume of distribution (V ss) of 320 L or 4.2 L/kg, a mean terminal elimination half-life (t ½) of 48 h, and a mean total clearance (CL) of 13.5 L/h. In a neutropenic murine thigh
infection model, the pharmacodynamic parameter that demonstrated the best correlation with antibacterial response was the ratio of area under the plasma concentration-time curve over 24 h to the minimum inhibitory concentration (AUC0-24h/MIC). Several animal model studies including mouse systemic
infection, thigh
infection, lung
infection, and
pyelonephritis models have been published and demonstrated the in vivo efficacy of
eravacycline. A phase II clinical trial evaluating the efficacy and safety of
eravacycline in the treatment of community-acquired complicated
intra-abdominal infection (cIAI) has been published as well, and phase III clinical trials in cIAI and complicated
urinary tract infection (cUTI) have been completed. The
eravacycline phase III program, known as IGNITE (Investigating Gram-Negative
Infections Treated with
Eravacycline), investigated its safety and efficacy in cIAI (IGNITE 1) and cUTI (IGNITE 2).
Eravacycline met the primary endpoint in IGNITE 1, while data analysis for IGNITE 2 is currently ongoing. Common adverse events reported in phase I-III studies included gastrointestinal effects such as
nausea and
vomiting.
Eravacycline is a promising intravenous and oral fluorocycline that may offer an alternative treatment option for patients with serious
infections, particularly those caused by multidrug-resistant Gram-negative pathogens.