New Xerava data presented at Annual Surgical Infection Society Meeting for treatment of complicated intra-abdominal infections

Tetraphase Pharmaceuticals, Inc announced the presentation of positive data from three studies further evaluating its lead compound, Xerava (eravacycline), a novel, fully-synthetic fluorocycline, approved by the FDA and the European Medicines Agency for the treatment of complicated intra-abdominal infections (cIAI), as well as data from a retrospective study of hospital-based outcomes in cIAI. These data were presented at the 39th Annual Surgical Infection Society (SIS) Meeting, held June 5-8, 2019 in Coronado, Calif.

Microbiology and Outcomes of Hospitalization With Intra-Abdominal Infections in the U.S. .: A Retrospective Cohort Study To better understand the microbiology and outcomes of hospitalization due to cIAIs, researchers performed a multicenter retrospective cohort study in the Premier database of approximately 180 hospitals from 2013-2017. All adult patients hospitalized with cIAI and a positive blood or abdominal culture were identified. Among 4,453 patients with cIAI and positive cultures, 3,771 (84.7%) had a Gram-negative and 1,782 (40.0%) had a Gram-positive organism identified. The majority of cases (n=2,941; 66.0%) were monomicrobial. Among patients with a polymicrobial infection, 1,118 (25.1%) had two organisms while 394 (8.8%) had three or more pathogens. Notably, resistance to third-generation cephalosporins occurred in 7.6% of all Gram-negative pathogens. The most common Gram-negative pathogens were E. coli (2,624; 58.9%) and K. pneumoniae (774; 17.4%). Beyond microbiology, this retrospective study analyzed hospitalization outcomes. Findings showed that hospital mortality due to cIAI was 7.6%, and 11.2% of patients were readmitted within 30 days of discharge. The median (interquartile range) length of stay was 6 (3, 12) days, and median total cost was $21,148 ($12,051, $43,637). These results highlight the significant morbidity and mortality associated with cIAI hospitalizations, as well as the substantial cost burden.

Efficacy of Eravacycline in Non-Appendiceal Complicated Intra-Abdominal Infections: An Analysis of Two Phase III Trials: Compared to complicated appendicitis, cIAIs of non-appendiceal etiology carry a higher risk for initial treatment failure, prolonged treatment duration, and increased mortality. Researchers hypothesized that patients with non-appendiceal cIAIs treated with Xerava would have similar clinical outcomes when compared to those treated with carbapenems. A post-hoc analysis of patients diagnosed with cIAI of non-appendiceal origin from two Phase III studies, IGNITE1 and IGNITE4, was performed to determine clinical outcomes. Clinical cure rates in patients diagnosed with complicated appendicitis were 89.0% and 88.6% in patients treated with Xerava and comparators, respectively. In patients with non-appendiceal cIAIs treated with Xerava and comparators, clinical cure rates were 88.8% and 89.7%, respectively. Across the non-appendiceal subgroups, clinical outcomes between Xerava and comparators were similar. This pooled analysis suggests that Xerava is an effective empiric treatment option for patients with cIAI, including those with specific higher-risk diagnoses such as peritonitis and intestinal perforation.

2017 Global Surveillance of the In Vitro Activity of Eravacycline Against Clinical Isolates From Gastrointestinal Infections: In a subset of data from a 2017 global surveillance study, 2,005 non-duplicate, non-consecutive, single-patient gastrointestinal isolates were analyzed to determine the Minimum Inhibitory Concentration (MIC) required to inhibit the growth of 50% and 90% of organisms, respectively, for Xerava and comparators. Results demonstrated potent in vitro activity against Enterobacteriaceae with an MIC90 value of 1 mg/L compared to 4 mg/L for tigecycline. Xerava demonstrated two- to eight-fold greater potency than tigecycline against Escherichia coli, Klebsiella spp. and Acinetobacter baumannii,including against pathogens expressing extended spectrum beta-lactamases (ESBL). In addition, Xerava had two- to four-fold greater potency than tigecycline versus clinically important Gram-positive pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus spp. These data support that Xerava is a treatment option for cIAI in patients who harbor or are at risk for infections due to resistant Enterobacteriaceae.

Factors That Impact Duration of Antibiotic Therapy From Phase III Studies of Eravacycline for Intra-Abdominal Infection : A post-hoc analysis of two pooled Phase III studies (IGNITE1 and IGNITE4) of Xerava examined the impact of certain patient-specific variables on duration of treatment. Researchers sought to determine whether variables associated with duration of treatment differed in patients based on the type of cIAI – complicated appendicitis or non-appendiceal infections. Patients with cIAI from both Phase III studies were randomized (1:1) to receive Xerava or a carbapenem. Duration of therapy was discretionary up to 14 days. Groups were categorized by the following durations: less than 5 days, 6-8 days and greater than 8 days. Results showed that among all patients, those who received longer treatment were older (p=0.004), sicker (p<0.001), more likely to have non-appendiceal infections (p<0.001) and to have undergone open surgery for infection source control (p<0.001). For patients with complicated appendicitis, open surgery and polymicrobial infection were associated with longer treatment (p<0.001), whereas patients with non-appendiceal infections who had longer length of therapy were more likely to be ill (p=0.029), to have undergone open surgery (p=0.001) and to have received prior antibiotics (p=0.001). Further analysis to quantify the impact of various factors in terms of days of therapy showed that patients who had laparoscopic surgery for source control had approximately one day less of therapy, while patients who had a multidrug-resistant Enterococcus pathogen received 1.3 additional days of therapy.