- |||||||||| prexasertib (ACR-368) / Acrivon Therap
Journal: Inhibition of Chk2 promotes neuroprotection, axon regeneration, and functional recovery after CNS injury. (Pubmed Central) - Sep 20, 2022
Inhibitors of ATM-Chk2, but not the parallel ATR-Chk1 pathway, also promote marked, functional recovery after acute central nervous system injury in rats, suggesting that inhibiting nonhomologous end-joining rather than homologous recombination is crucial for neuroprotection. We demonstrate that the Chk2 inhibitor, prexasertib, which has been evaluated in phase 2 clinical trials for cancer, has potent neuroprotective effects and represents a new treatment option to promote functional recovery after spinal cord or optic nerve injury.
- |||||||||| Xerava (eravacycline) / SOM Biotech, Ewha Womans University, PAION, Innoviva
ENDOBRONCHIAL ASPERGILLUS NIDULANS POSTLUNG TRANSPLANT (Convention Center Exhibit Hall: Rapid Area 1C) - Sep 11, 2022 - Abstract #CHEST2022CHEST_3580;
Patient was initially treated with Meropenem, then switched to Eravacycline targeting all three bacteria...Therapy usually includes oral itraconazole/voriconazole, with the role of inhaled amphotericin remains controversial although has been reported to be effective [1]. Aspergillus Nidulans is a rare colonizer of the endobronchial tree, especially in the immunocomprised host [2].
- |||||||||| Xerava (eravacycline) / SOM Biotech, Ewha Womans University, PAION, Innoviva, Zemdri (plazomicin) / Ionis, Achaogen
Journal: New antimicrobial treatment options for severe Gram-negative infections. (Pubmed Central) - Sep 10, 2022
Severe/MDR Gram-negative infections continue to be important infections due to their impact on patient outcomes, especially in critically ill and immunocompromised hosts. The availability of new antibiotics offers an opportunity to improve empiric and definitive treatment of these infections.
- |||||||||| Clinical data, Review, Journal: Clinical data from studies involving novel antibiotics to treat multidrug-resistant Gram-negative bacterial infections. (Pubmed Central) - Aug 24, 2022
Other clinically effective combinations include meropenem-vaborbactam (MVB), ceftolozane-tazobactam (C/T) and imipenem-relebactam (I-R)...Susceptible CRE infections can be treated with fluoroquinolones, aminoglycosides or fosfomycin, but alternatives include CZA, MVB, I-R, cefiderocol, tigecycline and eravacycline...Currently, no single agent can treat all MDR-GNB infections, but new β-lactam-β-lactamase inhibitor combinations are often effective for different infection sites, and, when used appropriately, have the potential to improve outcomes. This article reviews clinical studies investigating novel β-lactam approaches for treatment of MDR-GNB infections.
- |||||||||| prexasertib (ACR-368) / Acrivon Therap, cofetuzumab pelidotin (ABBV-647) / Pfizer, AbbVie, GSK461364 / GSK
Journal: Multiomics characterization implicates PTK7 in ovarian cancer EMT and cell plasticity and offers strategies for therapeutic intervention. (Pubmed Central) - Aug 22, 2022
Furthermore, using high-throughput drug sensitivity testing (525 drugs) we show that targeting PTK7 exhibited synergistic activity with chemotherapeutic agent paclitaxel, CHK1/2 inhibitor prexasertib, and PLK1 inhibitor GSK461364, among others, in OC cells and ex vivo primary samples. Taken together, our study provides unique insight into the function of PTK7, which helps to define its role in mediating aberrant Wnt signaling in ovarian cancer.
- |||||||||| Xerava (eravacycline) / SOM Biotech, Ewha Womans University, PAION, Innoviva
COMPLICATED CASE OF POLYMICROBIAL LOCULATED EMPYEMA CAUSING SEPTIC CARDIOMYOPATHY (Convention Center Exhibit Hall: Poster Area) - Aug 16, 2022 - Abstract #CHEST2022CHEST_2710;
Pleural fluid culture later grew multi-drug resistant Streptococcus pneumoniae and Enterobacter aerogenes, thus antibiotics were adjusted to eravacycline...With the positive inotropic effects of milrinone, TTE showed LVEF improvement to 40-45% and LVOT VTI of 15cm/stroke... Our case emphasizes the importance of maintaining a broad differential diagnosis and consideration of multifactorial processes occurring in parallel when treating a critically ill patient.
- |||||||||| Xerava (eravacycline) / SOM Biotech, Ewha Womans University, La Jolla Pharma, PAION
Preclinical, Journal: In vitro activity and adaptation strategies of eravacycline in clinical Enterococcus faecium isolates from China. (Pubmed Central) - Aug 12, 2022
In addition, a genetic mutation in 16 S rRNA (G190A) were detected in resistant E. faecium isolates induced by Erava. In summary, Erava exhibits potent in vitro antimicrobial activity against E. faecium, but mutation of Tet target sites and elevated expression of efflux pumps under Erava selection results in Erava resistance.
- |||||||||| Xerava (eravacycline) / SOM Biotech, Ewha Womans University, La Jolla Pharma, PAION
Clinical: I have to read it in more detail to understand this score. However, I feel that we still underestimate Enterococcus it's "low-virulence" compensate by its resilience. In high-risk patients, SOT (liver specially), biliary cancer, stents, etc, I add linezo or eravacycline (Twitter) - Aug 7, 2022
- |||||||||| Xerava (eravacycline) / SOM Biotech, Ewha Womans University, La Jolla Pharma, PAION
Review, Journal: Current and Potential Therapeutic Options for Infections Caused by Difficult-to-Treat and Pandrug Resistant Gram-Negative Bacteria in Critically Ill Patients. (Pubmed Central) - Jul 29, 2022
A focal point of the review focuses on salvage treatment, synergistic combinations (double and triple combinations), as well as increased exposure regimen adapted to the MIC of the pathogen. The most available data regarding novel antimicrobials, including novel β-lactam-β-lactamase inhibitor combinations, cefiderocol, and eravacycline as potential agents against DTR and PDR Gram-negative strains in critically ill patients are thoroughly presented.
- |||||||||| prexasertib (ACR-368) / Acrivon Therap, samotolisib (LY3023414) / Eli Lilly
Trial completion date, Metastases: ExIST: LY3023414 and Prexasertib in Metastatic Triple-negative Breast Cancer (clinicaltrials.gov) - Jul 20, 2022
P2, N=10, Active, not recruiting,
The most available data regarding novel antimicrobials, including novel β-lactam-β-lactamase inhibitor combinations, cefiderocol, and eravacycline as potential agents against DTR and PDR Gram-negative strains in critically ill patients are thoroughly presented. Trial completion date: Aug 2022 --> Dec 2022
- |||||||||| prexasertib (ACR-368) / Acrivon Therap
Small-molecule screen reveals synergy of cell cycle checkpoint kinase inhibitors with DNA-damaging chemotherapies in medulloblastoma (Forum) - Jul 19, 2022 - Abstract #EANO2022EANO_163;
P1
To identify the best-in-class, multiple different CHK1/2 inhibitors were compared and indicated that LY2606368 (prexasertib) had the strongest chemosensitizing activity in MB leading to further clinical investigation in th SJ-ELIOT clinical trial (NCT04023669). Moreover, these data demonstrate that we have developed a robust and collaborative preclinical assessment platform that can be used to identify potentially effective new therapies to be taken forward to the clinic for pediatric MB.
- |||||||||| Xerava (eravacycline) / SOM Biotech, Ewha Womans University, La Jolla Pharma, PAION
Journal: Eravacycline infusion-related hypoesthesia: A case report. (Pubmed Central) - Jul 13, 2022
This is a unique case of severe hypoesthesia secondary to ERV infusion leading to drug discontinuation. More data are needed to determine effective mitigation strategies.
- |||||||||| prexasertib (ACR-368) / Acrivon Therap, Xerava (eravacycline) / SOM Biotech, Ewha Womans University, La Jolla Pharma, PAION
Journal: A Study of Drug Repurposing to Identify SARS-CoV-2 Main Protease (3CLpro) Inhibitors. (Pubmed Central) - Jul 2, 2022
Among the three compounds, only eravacycline showed potential antiviral activities with no significant cytotoxicity. A further study is planned for pre-clinical trials.
- |||||||||| Xerava (eravacycline) / SOM Biotech, Ewha Womans University, La Jolla Pharma, PAION
Retrospective data, Journal: A Retrospective Multicenter Evaluation of Eravacycline Utilization in Community and Academic Hospitals. (Pubmed Central) - Jun 22, 2022
A further study is planned for pre-clinical trials. These results illustrate the potential versatility of eravacycline with a broad activity spectrum, good safety and tolerability profile, flexibility for use in patients with renal injury or antibiotic allergies, and positive clinical outcomes in this real-world cohort.
- |||||||||| Xerava (eravacycline) / SOM Biotech, Ewha Womans University, La Jolla Pharma, PAION, colistin sulphate / Generic mfg., Zemdri (plazomicin) / Ionis, Achaogen
I’d also then test imi, C-A, cefiderocol, I-R (+ C-T), plazomicin, eravacycline, colistin (essentially full court press) to begin planning my sequence of regimens (plan A, plan B, plan C) over the next year for this pt. That’s just my crazy ID pharmacist brain. 😅 Yay superbugs. (Twitter) - Jun 22, 2022
- |||||||||| tetracycline / Generic mfg.
Journal: Re-establishing the utility of tetracycline-class antibiotics for current challenges with antibiotic resistance. (Pubmed Central) - Jun 22, 2022
We also consider various scenarios of unmet clinical needs where patients might benefit from re-engagement with tetracycline-class antibiotics including outpatient treatment options, patients with known β-lactam antibiotic allergy, reducing the risk of Clostridioides difficile infection, and their potential as monotherapy in polymicrobial infections while minimising the risk of any potential drug-drug interaction. KEY MESSAGESThe long-standing safety profile and broad spectrum of activity of tetracycline-class antibiotics made them a popular choice for treatment of various bacterial infections; unfortunately, antimicrobial resistance has limited the utility of the early-generation tetracycline agents.The latest generation of tetracycline-class antibiotics, including eravacycline, tigecycline, and omadacycline, overcomes the most common acquired tetracycline resistance mechanisms.Based on in vitro characteristics and clinical data, these newer tetracycline agents provide an effective antibiotic option in the treatment of approved indications in patients with unmet clinical needs - including patients with severe penicillin allergy, with renal or hepatic insufficiency, recent Clostridioides difficile infection, or polymicrobial infections, and those at risk of drug-drug interactions.
- |||||||||| Preclinical, Review, Journal: Efficacy and In Vitro Activity of Novel Antibiotics for Infections With Carbapenem-Resistant Gram-Negative Pathogens. (Pubmed Central) - Jun 14, 2022
Furthermore, combinations of known β-lactams with recently developed β-lactam inhibitors, such as ceftazidime-avibactam, ceftolozane-tazobactam, ceftazidime-tazobactam, and meropenem-vaborbactam, has been suggested for the treatment of infections by extended-spectrum β-lactamases, carbapenemases, and AmpC producer bacteria. Nonetheless, they are not active against all carbapenemases, and there are reports of resistance to these combinations in clinical isolates.This review summarizes and discusses the in vitro and clinical evidence of the recently approved antibiotics, β-lactam inhibitors, and those in advanced phases of development for treating MDR infections caused by Gram-negative multi-drug resistant (MDR) bacterial species.
- |||||||||| Xerava (eravacycline) / SOM Biotech, Ewha Womans University, La Jolla Pharma, PAION
Controlling Bacterial Persister Cells by Targeting the Achilles' Heel of Dormancy (Exhibit and Poster Hall) - Jun 4, 2022 - Abstract #ASMMicrobe2022ASM_Microbe_2379;
In addition to planktonic cells, 100 µg/mL eravacycline reduced the number of viable biofilm cells of UPEC, P. aeruginosa PAO1, and P. aeruginosa PDO300 by 99.2 ± 0.5%, 99.9 ± 0.8%, and 99.6 ± 0.4%, respectively. Thus, while dormancy is a well-known cause of antibiotic tolerance, the associated reduction in drug efflux provides an Achilles' heel for controlling persister cells if given appropriate agent and treatment condition.
- |||||||||| Preclinical, Journal: Multicenter surveillance of in vitro activities of cefepime-zidebactam, cefepime-enmetazobactam, omadacycline, eravacycline, and comparator antibiotics against Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii complex causing bloodstream infection in Taiwan, 2020. (Pubmed Central) - May 29, 2022
The MIC ranges of the cefepime-zidebactam against carbapenemase-producing Enterobacterales isolates (irrespective of the carbapenemase type [MIC ≤ 4 mg/L]) and carbapenem-NS or ceftolozane-tazobactam-NS P. aeruginosa isolates (MIC value, 8 mg/L) were significantly lower than those of the cefepime-enmetazobactam. : The efficacy of novel antibiotics against important drug-resistant GNB must be monitored and validated during the clinical treatment of patients.
- |||||||||| prexasertib (ACR-368) / Acrivon Therap, samotolisib (LY3023414) / Eli Lilly
Enrollment closed, Metastases: ExIST: LY3023414 and Prexasertib in Metastatic Triple-negative Breast Cancer (clinicaltrials.gov) - May 26, 2022
P2, N=10, Active, not recruiting,
: The efficacy of novel antibiotics against important drug-resistant GNB must be monitored and validated during the clinical treatment of patients. Recruiting --> Active, not recruiting
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