GC-072: A Novel Therapeutic Candidate for Oral Treatment of Melioidosis and Infections Caused by Select Biothreat Pathogens.

GC-072: A Novel Therapeutic Candidate for Oral Treatment of Melioidosis and Infections Caused by Select Biothreat Pathogens. Antimicrob Agents Chemother. 2019 Sep 23;: Authors: Shearer JD, Saylor ML, Butler CM, Treston AM, Heine HS, Chirakul S, Schweizer HP, Louie A, Drusano GL, Zumbrun SD, Warfield KL Abstract Burkholderia pseudomallei (B. pseudomallei), the etiological agent of melioidosis, is a Gram-negative bacterium with additional concern as a biothreat pathogen. The mortality rate from B. pseudomallei varies depending on the type of infection and extent of available health care, but in the case of septicemia left untreated it can range from 50 - 90%. Current therapy for melioidosis is biphasic, consisting of parenteral acute-phase treatment for two weeks or longer, followed by oral eradication-phase treatment lasting several months. An effective oral therapeutic for outpatient treatment of acute-phase melioidosis is needed. GC-072 is a potent, 4-oxoquinolizine antibiotic with selective inhibitory activity against bacterial topoisomerases. GC-072 has demonstrated in vitro potency against susceptible and drug-resistant strains of B. pseudomallei and is also active against Burkholderia mallei, Bacillus anthracis, Yersinia pestis, and Francisella tularensis GC-072 is bactericidal both extra- and intracellularly, with rapid killing noted within a few hours and reduced development of resistance compared to ceftazidime. GC-072, delivered intragastrically...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research

Related Links:

We examined the role of interleukin-10 (IL-10) in resolution of neuropathic pain induced by cisplatin. In search of an underlying mechanism, we studied the effect of cisplatin and IL-10 on spontaneous activity (SA) in dorsal root ganglia neurons. Cisplatin (2 mg/kg daily for 3 days) induced mechanical hypersensitivity that resolved within 3 weeks. In both sexes, resolution of mechanical hypersensitivity was delayed in Il10−/− mice, in WT mice treated intrathecally with neutralizing anti-IL-10 antibody, and in mice with cell-targeted deletion of IL-10R1 on advillin-positive sensory neurons. Electrophysiologicall...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research
This study examined whether NR also blunts the loss of intraepidermal nerve fibers induced by paclitaxel, which is associated with peripheral neuropathy. The work was conducted in female rats with N-methyl-nitrosourea (MNU)-induced tumors of the mammary gland to increase its translational relevance, and to assess the interaction of NR with paclitaxel and NR's effect on tumor growth. Once daily oral administration of 200 mg/kg NR p.o. beginning with the first of 3 i.v. injections of 6.6 mg/kg paclitaxel to tumor-bearing rats significantly decreased paclitaxel-induced hypersensitivity to tactile and cool stimuli, as well as ...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research
We describe a case of an otherwise healthy, community-dwelling man who presented with subacute cavitary lung disease, the causative organism of which turned out to be Burkholderia cepacia complex.  Our report is accompanied by a review of the literature, which identified an additional eleven cases in the same category.  We analyze all of the available cases for the emergence of any identifiable patterns or peculiarities. PMID: 32959626 [PubMed - in process]
Source: Monaldi Archives for Chest Disease - Category: Respiratory Medicine Tags: Monaldi Arch Chest Dis Source Type: research
In conclusion, inhibition of PK signaling with PC1 prevented the neurotoxic effects of chemotherapeutics, suggesting a promising strategy for neuroprotective therapies against the sensory neuron damage induced by exposure to these drugs.
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusions: We demonstrated the prognostic value of some dose–volume parameters, although in a retrospective series, this is potentially useful to improve planning procedure. In addition, for the first time in a non-endemic area, a threshold value of GTVT, prognostic for LC, has been confirmed.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Treatment options as second-line therapy for advanced ureteral carcinoma are limited, and patients experiencing recurrence after first-line cisplatin-based chemotherapy have a poor prognosis. Recently, the programmed death-1 (PD-1) inhibitor pembrolizumab provided a better survival benefit with a complete response rate (9.2%) for chemoresistatant urothelial carcinoma. However, the dynamic changes of the cancer microenvironment about the cases of complete response are still unknown. We herein report a case of a 57-year-old man who had been diagnosed with localized, non-muscle-invasive bladder cancer (pT1N0M0, high grade), f...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
The bone marrow (BM) exists heterogeneously as hematopoietic/red or adipocytic/yellow marrow depending on skeletal location, age, and physiological condition. Mouse models and patients undergoing radio/chemotherapy or suffering acute BM failure endure rapid adipocytic conversion of the marrow microenvironment, the so-called “red-to-yellow” transition. Following hematopoietic recovery, such as upon BM transplantation, a “yellow-to-red” transition occurs and functional hematopoiesis is restored. Gold Standards to estimate BM cellular composition are pathologists' assessment of hematopoietic cellularit...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
In this study, the therapeutic potential of combinations of an antibiotic and a broad-spectrum antimicrobial peptide (AMP) was evaluated against five bacterial biothreats, the etiologic agents of glanders (Burkholderia mallei), melioidosis (Burkholderia pseudomallei), plague (Yersinia pestis), tularemia (Francisella tularensis), and anthrax (Bacillus anthracis). The therapeutics included licensed early generation antibiotics which are now rarely used. Three antibiotics and one 24- amino acid AMP were selected based on MIC assay data. Combinations of the AMP and tigecycline, minocycline, or novobiocin were screened for syne...
Source: Microbial Pathogenesis - Category: Infectious Diseases Source Type: research
Abstract To improve the preparedness against exposure to highly pathogenic bacteria and to anticipate the wide variety of bacteria that can cause bloodstream infections (BSIs), a safe, unbiased and highly accurate identification method was developed. Our liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based method can identify highly pathogenic bacteria, their near-neighbors and bacteria that are common causes of BSIs directly from positive blood culture flasks. The developed Peptide-Based Microbe Detection Engine (http://proteome2pathogen.com) relies on a two-step workflow: a genus-level search followed...
Source: International Journal of Medical Microbiology - Category: Microbiology Authors: Tags: Int J Med Microbiol Source Type: research
Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) sample preparation methods, including the direct, on-plate formic acid, and ethanol/formic acid tube extraction methods, were evaluated for their ability to render highly pathogenic organisms nonviable and safe for handling in a biosafety level 2 laboratory. Of these, the tube extraction procedure was the most successful, with none of the tested strains surviving this sample preparation method. Tube extracts from several agents of bioterrorism and their near neighbors were analyzed in an eight-laboratory study to examine the u...
Source: Journal of Clinical Microbiology - Category: Microbiology Authors: Tags: Bacteriology Source Type: research
More News: Anthrax | Burkholderia | Burkholderia Mallei | Burkholderia Pseudomallei | Chemotherapy | Glanders | Health Management | Microbiology | Yersinia