Additional Data Points to Potential of XERAVA to Treat Carbapenem-Resistant, Multidrug-Resistant Escherichia Coli
TP-6076 Demonstrates In Vivo Efficacy in Murine Lung and Thigh Infection Models with Acinetobacter Baumannii
“The data presented at ASM Microbe underscore the broad potential of XERAVA as a potent antibiotic against gram-negative and gram-positive clinical isolates, including MDR pathogens,” said
Studies Continue to Demonstrate the Potent In Vitro Activity of Eravacycline Against Gram-Negative and Gram-Positive Clinical Isolates, Including Multidrug-Resistant Pathogens
Carbapenem resistance is emerging in E. coli, including its MDR lineage. New agents, including XERAVA, have distinctive mechanisms that inhibit or kill many carbapenem-resistant organisms. Accordingly, Johnson et al. tested these antibiotics against clinical E. coli isolates, including those that are carbapenem resistant, from surveillance systems encompassing multiple sites across the U.S. The minimum inhibitory concentrations (MIC) of 179 U.S. clinical E. coli isolates, which were non-susceptible to one or more carbapenems, were determined with cefiderocol, ceftazidime-avibactam and XERAVA; three carbapenems (meropenem,imipenem, ertapenem); and eight non-carbapenem comparators. Using
In a large, ongoing surveillance study of XERAVA, researchers evaluated the in vitro activity of the drug against Gram-negative and Gram-positive global isolates collected in 2017, including MDR pathogens. A total of 7,084 bacterial isolates were collected from different geographic regions, including
In an additional XERAVA study, up to 15 hospitals submitted pathogens collected from 2014-2018 from patients attending hospital clinics, emergency rooms, medical and surgical wards, and intensive care units as part of CANWARD, an ongoing national
Additional posters highlighted ways to evaluate XERAVA using the Beckman Coulter MicroScan Dried Gram-Negative MIC Panels and the bioMérieux ETEST®. The ETEST strip and the MicroScan Dried Gram-Negative MIC panel containing XERAVA were each shown to correlate well with MICs obtained by broth microdilution reference method (BMD). Both methods could represent a valuable tool for XERAVA susceptibility testing and an alternative to the BMD reference method.
New Data on the Pharmacokinetics and Efficacy of TP-6076 in the Murine Lung and Thigh Infection Models with A. baumannii
In addition to the XERAVA findings, new data on TP-6076, Tetraphase’s Phase 2 ready candidate for MDR Gram-negative bacteria, such as carbapenem-resistant Enterobacteriaceae and carbapenem-resistant Acinetobacter baumanii, were presented. These resistant organisms, particularly MDR A. baumannii, are of increasing concern in association with ventilator-associated pneumonia with high morbidity and mortality rates, especially in immunocompromised patients.
Studies were performed to evaluate the efficacy of TP-6076 in murine lung infection and murine thigh infection models against MDR A. baumannii clinical isolates. TP-6076 demonstrated high potency against MDR A. baumannii clinical isolates that were used in these in vitro models, with MICs that ranged from <0.008 - 0.25 ug/mL (MIC 90 = 0.0625 ug/mL).
Results of the first study indicated TP-6076’s ability to penetrate the lung. Single IV doses of TP-6076 (0.25 – 40 mg/kg) were administered to neutropenic (or immunocompromised) mice, and epithelial-lining fluid (ELF) was subsequently evaluated. TP-6076 resulted in statistically significant reductions in bacterial lung titers in the murine lung infection model, with A. baumannii lung colony forming units (CFU) decreasing by 2.4 – 6.2 log10 CFU when compared to the untreated control group. In comparison, tigecycline resulted in a 0.2 – 4.2 log10 CFU reduction in mean lung titers.
TP-6076’s in vivo efficacy was also demonstrated in an immunocompromised murine thigh infection model with A. baumannii. Female neutropenic mice were infected intramuscularly with MDR A. baumannii clinical isolates into their right hind-limb thighs. TP-6076 doses resulted in a statistically significant reduction (p<0.0001) in mean thigh CFU to 3.0 – 3.8 log10 CFU, compared to the untreated controls. Doses of tigecycline resulted in less than a 2 log10 CFU reduction observed for most isolates, which was not statistically significant.
The results of these studies demonstrated in vitro activity of TP-6076 against MDR A. baumannii isolates with statistically significant reductions in bacterial tissue titers in the murine thigh and lung infection models and suggest that TP-6076 has the potential to treat life-threatening multi-drug resistant A. baumannii infections, including ventilator-associated pneumonia.
XERAVA(eravacycline for injection) is a tetracycline class antibacterial indicated for the treatment of complicated intra-abdominal infections (cIAI) in patients 18 years of age and older. XERAVA was investigated for the treatment of cIAI as part of the Company's IGNITE (Investigating Gram-Negative Infections Treated with Eravacycline) Phase 3 program. In the first pivotal Phase 3 trial in patients with cIAI, twice-daily intravenous (IV) XERAVA met the primary endpoint by demonstrating statistical non-inferiority of clinical response compared to ertapenem and was well-tolerated. In the second Phase 3 clinical trial in patients with cIAI, twice-daily IV XERAVA met the primary endpoint by demonstrating statistical non-inferiority of clinical response compared to meropenem and was well-tolerated. In both trials, XERAVA achieved high cure rates in patients with Gram-negative pathogens, including resistant isolates.
Indications and Usage
XERAVA is indicated for the treatment of complicated intra-abdominal infections (cIAI) caused by 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 patients 18 years or older.
Limitations of Use
XERAVA is not indicated for the treatment of complicated urinary tract infections (cUTI).
To reduce the development of drug-resistant bacteria and maintain the effectiveness of XERAVA and other antibacterial drugs, XERAVA should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Important Safety Information
XERAVA is contraindicated for use in patients with known hypersensitivity to eravacycline, tetracycline-class antibacterial drugs, or to any of the excipients. Life-threatening hypersensitivity (anaphylactic) reactions have been reported with XERAVA.
The use of XERAVA during tooth development (last half of pregnancy, infancy and childhood to the age of eight years) may cause permanent discoloration of the teeth (yellow-gray-brown) and enamel hypoplasia.
The use of XERAVA during the second and third trimester of pregnancy, infancy and childhood up to the age of eight years may cause reversible inhibition of bone growth.
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents and may range in severity from mild diarrhea to fatal colitis.
The most common adverse reactions observed in clinical trials (incidence ≥3%) were infusion site reactions (7.7%), nausea (6.5%), and vomiting (3.7%).
XERAVA is structurally similar to tetracycline-class antibacterial drugs and may have similar adverse reactions. Adverse reactions including photosensitivity, pseudotumor cerebri, and anti-anabolic action which has led to increased BUN, azotemia, acidosis, hyperphosphatemia, pancreatitis, and abnormal liver function tests, have been reported for other tetracycline-class antibacterial drugs, and may occur with XERAVA. Discontinue XERAVA if any of these adverse reactions are suspected.
To report SUSPECTED ADVERSE REACTIONS, contact
Please see full Prescribing Information for XERAVA at www.XERAVA.com.
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