Objectives: Clinical resistance to the currently recommended extended-spectrum cephalosporins (ESCs), the last remaining options for empirical antimicrobial monotherapy of gonorrhoea globally, has been reported. New antimicrobials are essential to avoid the emergence of untreatable gonorrhoea. We have investigated the in vitro activity of a novel dual bacterial topoisomerase inhibitor of the ATPase activities of GyrB and ParE (Vertex aminobenzimidazole VT12-008911), compared with antimicrobials currently or previously recommended for gonorrhoea treatment.
Methods: MICs were determined using agar dilution (VT12-008911) or Etest (seven antimicrobials) for international reference strains (n = 28) and clinical Neisseria gonorrhoeae isolates (n = 220). The latter included three extensively drug-resistant isolates with high-level ceftriaxone resistance, additional isolates with clinical ESC resistance and a high number of isolates with ciprofloxacin resistance and multidrug resistance.
Results: The MIC(50), MIC(90) and MIC range of VT12-008911 were 0.064, 0.125 and ≤0.002-0.25 mg/L, respectively. One-hundred and seventy (69%) isolates were ciprofloxacin resistant; however, only 54 of those isolates had a VT12-008911 MIC >0.064 mg/L (47 and 7 with MIC = 0.125 mg/L and MIC = 0.25 mg/L, respectively). The in vitro activity of VT12-008911 was superior to that of ciprofloxacin and all additional antimicrobials investigated. Time-kill curve analysis showed that VT12-008911 exhibited potent time-dependent bactericidal activity, at or very close to the MIC, against N. gonorrhoeae.
Conclusions: In vitro results suggest that VT12-008911 might be an effective treatment option for gonorrhoea. However, it will be important to detail the pharmacokinetics/pharmacodynamics, toxicity, selection and mechanisms of VT12-008911 resistance in N. gonorrhoeae and, finally, to perform well-designed in vivo randomized clinical trials.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1093/jac/dku073 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Kurarinone Mitigates LPS-Induced Inflammatory Osteolysis by Inhibiting Osteoclastogenesis Through the Reduction of ROS Levels and Suppression of the PI3K/AKT Signaling Pathway.
Inflammation
January 2025
The Key Laboratory of Spine and Spinal Cord Disease of Jiangxi Province, Nanchang, 330006, China.
Inflammatory bone resorption represents a pathological condition marked by an increase in bone loss, commonly associated with chronic inflammatory conditions such as rheumatoid arthritis and periodontitis. Current therapies primarily focus on anti-inflammatory drugs and bisphosphonates; however, these treatments are limited due to side effects, inadequate efficacy, and unpredictable long-term complications. Kurarinone (KR), a bioactive compound isolated from the traditional Chinese herb Sophora flavescens, exhibits a range of biological activities, including anti-inflammatory, anticancer, and cardiovascular protective effects.
View Article and Find Full Text PDFPhyto-Fingerprinting of Putranjiva roxburghii Wall. Leaf Extract and its In Vitro Anti-Inflammatory Activity.
Cell Biochem Biophys
January 2025
Department of Zoology, MMV, Banaras Hindu University, Varanasi, 221005, UP, India.
Putranjiva roxburghii is an important medicinal plant utilized for remedy of female reproductive ailments. Its seed extract is being used as a uterine health booster due to the presence of several pharmaceutically important phytochemicals. However, the presence of phytochemicals in its leaf is still unexplored.
View Article and Find Full Text PDFPETRICCS Guideline Protocol: A Call to Improve Reporting Standards in Cell Culture Research.
J Oral Pathol Med
January 2025
Laboratory of Oral Histopathology, Health Sciences Faculty, University of Brasília, Brasília, Brazil.
Background: Cell culture studies play an important role in addressing fundamental scientific questions. However, inadequate reporting of these studies results in a lack of transparency and reproducibility. Recognizing the need for improvement, several ongoing efforts, such as CRIS guidelines and the ICLAC checklist, are focused on enhancing best practices for in vitro studies.
View Article and Find Full Text PDFTargeted editing of CCL5 with CRISPR-Cas9 nanoparticles enhances breast cancer immunotherapy.
Apoptosis
January 2025
Department of Breast Cancer Surgery, Jiangxi Cancer Hospital & Institute, Jiangxi Clinical Research Center for Cancer, The Second Affiliated Hospital of Nanchang Medical College, Jiangxi Key Laboratory of Oncology, No. 519 Beijing East Road, Nanchang, Jiangxi, 330029, China.
Breast cancer remains one of the leading causes of cancer-related mortality among women worldwide. Immunotherapy, a promising therapeutic approach, often faces challenges due to the immunosuppressive tumor microenvironment. This study explores the innovative use of CRISPR-Cas9 technology in conjunction with FCPCV nanoparticles to target and edit the C-C Motif Chemokine Ligand 5 (CCL5) gene, aiming to improve the efficacy of breast cancer immunotherapy.
View Article and Find Full Text PDFInhibition of transcriptional regulation of detoxification genes contributes to insecticide resistance management in Spodoptera exigua.
Commun Biol
January 2025
Key Laboratory of Integrated Management of Crop Diseases and Pests (Ministry of Education), College of Plant Protection, Nanjing Agricultural University, Nanjing, China.
Synthetic insecticides have been widely used for the prevention and control of disease vectors and agricultural pests. However, frequent uses of insecticides have resulted in the development of insecticide resistance in these insect pests. The resistance adversely affects the efficacy of insecticides, and seriously reduces the lifespan of insecticides.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!