By Emily Mui, PharmD

Infectious Disease Pharmacist, Stanford Healthcare

Dr. Mui reports no financial relationships relevant to this field of study.

Eravacycline is a novel fluorocycline antibiotic under the tetracycline antibacterial class. With a modified fluorine atom at the C7 position and pyrrolidinoacetamido group at the C9 position, eravacycline retains activity against tetracycline-specific resistance mechanisms.1 Eravacycline binds to the 30S ribosomal subunit, which results in disruption of bacterial protein synthesis. Eravacycline is FDA approved for the treatment of complicated intra-abdominal infections that are caused by the following susceptible microorganisms: Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, Enterobacter cloacae, Klebsiella oxytoca, Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, Streptococcus anginosus group, Clostridium perfringens, Bacteroides species, and Parabacteroides distasonis.

In Phase 3 clinical trials (IGNITE1 and IGNITE4), researchers found eravacycline to be noninferior to ertapenem and meropenem for the treatment of complicated intra-abdominal infections with the primary endpoint of clinical response in the micro-ITT population.2,3 However, eravacycline did not demonstrate noninferiority in the complicated urinary tract infection Phase 3 studies (IGNITE 2 and IGNITE 3) and carries a warning against its use for treatment of complicated urinary tract infections.

Table 1: Eravacycline Is Shown to Be Active Against Most Isolates of the Following Organisms in In-Vitro and Clinical Trials

Gram-Positive Bacteria

Gram-Negative Bacteria

  • Enterococcus faecalis
  • Enterococcus faecium
  • Staphylococcus aureus
  • Streptococcus anginosus group
  • Citrobacter freundii
  • Enterobacter cloacae
  • Escherichia coli
  • Klebsiella oxytoca
  • Klebsiella pneumoniae

Gram-Positive Anaerobic Bacteria

Gram-Negative Anaerobic Bacteria

  • Clostridium perfringens
  • Bacteroides caccae
  • Bacteroides fragilis
  • Bacteroides ovatus
  • Bacteroides thetaiotaomicron
  • Bacteroides uniformis
  • Bacteroides vulgatus
  • Parabacteroides distasonis


Eravacycline has a broad range of activity against many Gram-positive and Gram-negative aerobic and anaerobic organisms, including those that harbor multidrug resistance mechanisms, such as extended-spectrum beta-lactamase (ESBLs), carbapenem-resistant Enterobacteriaceae, carbapenem-resistant Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and anaerobes.

Compared to tigecycline, eravacycline is more than twice as potent against Gram-negative bacilli and Gram-positive cocci.4 Gram-negative organisms found to have lower MICs include A. baumannii, A. lwoffii, C. freundii, E. aerogenes, K. oxytoca, M. catarrhalis, M. morganii, P. mirabilis, P. vulgaris, P. stuartii, Salmonella spp., S. marcescens, and S. maltophilia, as well as certain panels with I/R phenotypes for third-generation cephalosporins. A greater than two-fold potency for eravacycline was seen for the following Gram-positive organisms: E. faecalis (VRE and VSE), E. faecium (VRE), Enterococcus spp., S. aureus (MRSA), coagulase-negative staphylococci (methicillin sensitive), S. pneumoniae, S. pyogenes, S. anginosus, S. intermedius, and S. mitis. Like tigecycline, eravacycline does not have activity against Pseudomonas aeruginosa.


Eravacycline resistance is associated with upregulation of nonspecific intrinsic multidrug-resistant efflux and target site modifications to the 16S rRNA or 30S ribosomal proteins.1 The C7 and C9 modification allow eravacycline to retain activity against organisms that carry certain tetracycline-specific resistance mechanisms, such as efflux mediated by tet(A), tet(B), and tet(K), and ribosomal protection ended by tet(M) and tet(Q).1


Absorption: Although not marked as an oral medication, in healthy volunteer studies, the oral bioavailability was approximately 28%.5


  • Protein binding: 79-90%;
  • Plasma concentration range: 100-10,000 mcg/mL;
  • Steady state volume of distribution: 321 L;
  • Steady state achieved in 5-7 days.

Metabolism: CYP3A4- and FMO-mediated oxidation;

Elimination: Renal elimination: 34% (20% as unchanged drug);

Feces Excretion: 47% (17% as unchanged drug).

Eravacycline is only available as an intravenous formulation. In earlier dose experimental studies, the oral bioavailability of eravacycline was approximately 28%.5 Eravacycline is highly protein bound with a volume of distribution that is a large steady state volume of distribution. In rabbit PK studies, the mean tissue concentrations are highest in renal cortex > liver > renal medulla > gallbladder > spleen > psoas muscle > lungs > bone marrow > pancreas > heart > vena cava > brain.6 Eravacycline is metabolized by CYP3A4- and FMO-mediated oxidation. About 34% of the dose is excreted in the urine and 47% is excreted in feces.1

The pharmacokinetic/pharmacodynamic parameter that best correlates with efficacy is area under the plasma concentration-time curve to the minimum inhibitory concentration (AUC:MIC).1

Dosage and Administration

Adjust dosing frequency for Child-Pugh Score C hepatic impairment. Dose adjustment is not required for renal impairment.

Table 2: Renal Impairment

Estimated CrCL (mL/min)


CrCL ≥ 90 mL/min

1 mg/kg (total body weight) every 12 hours

60-90 mL/min

No adjustment

30-60 mL/min

No adjustment

15-30 mL/min

No adjustment

Table 3: Hepatic Impairment

Child-Pugh Score



No adjustment


No adjustment


1 mg/kg Q12H on day 1, then
1 mg/kg Q24H on day 2

Adverse effects/Warnings

The most common side effect of eravacycline in Phase 3 clinical trials included infusion site reactions (7.7%), nausea (6.5%), vomiting (3.7%), and diarrhea (2.3%). The most common side effects leading to discontinuation of therapy were gastrointestinal.

The use of eravacycline should be avoided in patients who have known hypersensitivity to the tetracycline class antibacterial. Tooth discoloration and enamel hypoplasia may occur if eravacycline is administered during tooth development because this is a known adverse reaction of the tetracycline antimicrobial class. Tetracyclines also are known to form a stable calcium complex to bone-forming tissue and may result in a decrease in growth rate of the fibula. The safety and efficacy of eravacycline has not been established in pediatric patients; therefore, the same precautions for tetracycline class medications should be considered with eravacycline in the pediatric population.

Drug interactions

Eravacycline is metabolized primarily by CYP3A4. Concomitant use of strong CYP3A4 inducers, such as rifampin, can decrease eravacycline AUC by 35% and increase eravacycline clearance by 54%. Concomitant use of itraconazole (a strong CYP3A inhibitor) increased eravacycline Cmax by 5% and AUC by 32%, and decreased eravacycline clearance by 32%.

Pregnancy and lactation

  • In animal studies, eravacycline crosses the placenta and is found in fetal plasma. Eravacycline administration during the organogenesis period was associated with decreased ossification and fetal body weight and increased post-implantation loss.1
  • Eravacycline is excreted in milk in lactating rats; however, the extent of absorption in human infants is unknown.1


Eravacycline is a novel tetracycline antibiotic recently approved for the treatment of complicated intra-abdominal infections. It is unaffected by the two acquired tetracycline-specific resistance mechanisms (efflux pumps and ribosomal protection). It has broad antimicrobial activity against several MDR organisms, such as CREs, ESBLS, MRSA, VRE, and MDR Acinetobacter. It is unknown how eravacycline compares to tigecycline in the clinical setting, but it does appear to have a more favorable safety profile. 


  1. Tetraphase Pharmaceuticals Inc. XERAVA [prescribing information]. 2018. Available at: Accessed Feb. 12, 2019.
  2. Solomkin JS, Gardovskis J, Lawrence K, et al. IGNITE4: Results of a Phase 3, randomized, multicenter, prospective trial of eravacycline vs. meropenem in the treatment of complicated intra-abdominal infections. Clin Infect Dis 2018; Dec 18. doi: 10.1093/cid/ciy1029. [Epub ahead of print].
  3. Solomkin J, Evans D, Slepavicius A, 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;152:224-232.
  4. 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;57:5548-5558.
  5. Leighton A, Zupanets I, Bezugla N. Broad-spectrum fluorocycline PT-434 has oral bioavailability in humans. In: Milan; 2011.
  6. Petraitis V, Petraitiene R, Maung BBW, et al. Pharmacokinetics and comprehensive analysis of the tissue distribution of eravacycline in rabbits. Antimicrob Agents Chemother 2018;62. doi: 10.1128/AAC.00275-18.