Eravacycline is a novel, fully synthetic fluorocycline antibiotic with in vitro activity against aerobic and anaerobic Gram-positive and Gram-negative pathogens, including multidrug-resistant (MDR) bacteria. The pharmacokinetics (PK), urinary excretion, and safety/tolerability of intravenous (i.v.) eravacycline were evaluated in single- and multiple-ascending-dose studies.

BACKGROUND & AIMS:Digestive diseases represent a diverse group of clinical conditions that impact the population.Their heterogeneity in classification, presentation, acuity, chronicity, and need for drug therapy presents a challenge when comparing and contrasting the burden associated with these conditions. Prior studies use an outdated classification system and aggregate costs at the population level or focus on specific diseases, limiting the ability to characterize the overall landscape. Our aim was to provide the most up-to-date assessment of cost, utilization, and prevalence associated with digestive diseases. METHODS:We examined digestive disease claims and payment data for a commercially insured adult population between 2016 and 2018 to provide a comprehensive summary of costs, utilization, and prevalence across 38 conditions. Outcome variables included point prevalence and relative prevalence, annualized all-cause medical and drug costs, digestive disease-specific average medical cost, digestive disease-specific cost per fill, and utilization by clinical setting and by clinical condition. RESULTS:A total of 7,297,435 individuals with a digestive disease diagnosis were included in the study. The point prevalence of having a digestive disease in the total population was 24%.

Eravacycline is a novel, fully synthetic fluorocycline that is approved for the treatment of complicated intra-abdominal infections (cIAI) in adult patients. We report results from three studies in healthy subjects that investigated the distribution, metabolism, and excretion of intravenous (i.v.) eravacycline and the effect of a CYP3A4 inhibitor (itraconazole) and inducer (rifampin) on the pharmacokinetics (PK) of i.v. eravacycline. In the mass balance study, the majority of total radioactivity from [14C]eravacycline was recovered in the feces, suggesting biliary/fecal elimination is the major route of excretion for eravacycline and its metabolites after IV administration. The volume of distribution (217 liters) was greater than that of extracellular fluid, which suggests distribution beyond the central compartment. In the drug-drug interaction studies, mean area under the concentration-time curve from 0 h to the last time point (AUC0–t) and half-life were increased approximately 30% to 40% after a concomitant dose of i.v. eravacycline and itraconazole and clearance (CL) was decreased. A reduction in total eravacycline exposure (AUC) of approximately 25% to 35% and an increase in CL of approximately 50% occurred with concomitant eravacycline and rifampin treatment. The dose of eravacycline should be increased to 1.5 mg/kg of body weight every 12 h when coadministered with a strong CYP3A inducer.

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Aim: Recently approved for use in complicated intra-abdominal infection, eravacycline is a novel fluorocycline with broad spectrum of activity against resistant Gram-negative pathogens. This manuscript is a pooled analysis of two Phase III trials. Clinical efficacy: Clinical cure rates were 86.8% for eravacycline versus 87.6% for ertapenem, and 90.8% for eravacycline versus 91.2% for meropenem in the Intent to Treat (micro-ITT) populations, and 87.0% for eravacycline versus 88.8% ertapenem, and 92.4 versus 91.6% for meropenem in the Modified Intent to Treat (MITT) populations. Safety: Eravacycline is well tolerated, with lower rates of nausea, vomiting and diarrhea than other tetracyclines. Conclusion: Eravacycline is an effective new option for use in complicated intra-abdominal infections, and in particular, for the treatment of extended-spectrum β-lactamase- and carbapenem-resistant Enterobacteriaceae-expressing organisms.