Shubhangi Kansal

The rise in multidrug resistance in Klebsiella pneumoniae is an alarming issue, especially in invasive infections among patients with co-morbidities. With the gain of hypervirulence traits, multidrug-resistant K. pneumoniae has led to a significant increase in chronic infections and associated mortality. This study aims to explore the distribution of multidrug-resistant and hypervirulent (hv) K. pneumoniae in invasive infections in a tertiary care hospital. A total of 231 K. pneumoniae isolates were collected over a period of six months from invasive infections. These isolates were tested phenotypically and genotypically for the presence of antimicrobial resistance, along with molecular detection of hypervirulence determinants (iucA, rmpA, rmpA2, peg344, iroB). High levels of resistance to β-lactams, fluoroquinolones, and aminoglycosides were observed. Carbapenemase-encoding genes were widely distributed, and 22% showed the presence of at least one hypervirulence gene, most commonly iucA and rmpA. Co-carriage of resistance and hypervirulence determinants in K. pneumoniae was observed in nearly 20% of the isolates, indicating the emergence of MDR-hvKP phenotypes in the hospital setting. Mortality was significantly higher among patients infected with MDR isolates, whereas hypervirulence markers were not independently associated with mortality. The presence of MDR–hypervirulent strains remains clinically concerning and underscores the need for continued genomic surveillance.

The escalating threat of antimicrobial resistance (AMR), particularly among gram-negative pathogens, necessitates the development of novel therapeutic agents. Tridecaptins, a class of non-ribosomally synthesized lipopeptides with a novel mode of action, have garnered renewed interest in the fight against AMR. Our group previously identified tridecaptin M, a compound with a promising safety profile, prompting further investigation into its efficacy and preclinical characteristics. Here, we show that tridecaptin M exhibits potent activity against multidrug-resistant (MDR) Klebsiella pneumoniae and Escherichia coli without cross-resistance to colistin. It effectively inhibits biofilm formation and disrupts 50% of established biofilm at 10 µg/mL. Tridecaptin M demonstrates a favorable safety profile, as it does not inhibit the cardiac hERG channel and shows minimal interaction with cytochrome P450 enzymes, with no IC₅₀ detected up to 44.6 µg/mL. In vivo toxicity studies via subcutaneous administration confirm its safety up to 600 mg/kg, whereas intravenous administration reveals acute toxicity at ≥30 mg/kg, with biochemical evidence of skeletal muscle, cardiac, and hepatic involvement. In mouse infection models using a colistin-resistant MDR strain of K. pneumoniae reveal the in vivo potential of tridecaptin M and a dose-dependent efficacy at 10 mg/kg, 20 mg/kg, 50 mg/kg, and 100 mg/kg doses, showing a non-linear relationship. Tridecaptin M is metabolized by liver microsomes, with low clearance, and pharmacokinetic analysis in rats indicates favorable attributes, with a terminal half-life (T₁/₂) of 3.65 h intravenously and 8.81 h subcutaneously. Collectively, these data support the continued preclinical development of tridecaptin M as a promising candidate for treating severe gram-negative infections.

Aim: The aim of the study was to assess and evaluate the antimicrobial effectiveness of chitosan nanoparticles (CSNPs) with calcium hydroxide in the elimination of Enterococcus faecalis . Materials and Methods: Using the broth microdilution method, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of calcium hydroxide and CSNPs were measured. The antibiofilm effect of calcium hydroxide and CSNPs against E. faecalis biofilm was qualitatively analyzed using a crystal violet assay. A 7-day-old biofilms of E. faecalis grown on dentine discs were assigned to the following three groups ( n = 11 dentine discs), normal saline (group I), calcium hydroxide (group II), and CSNPs (group III). Quantification of live and dead cells using confocal microscopy was done to evaluate the antibiofilm efficacy of the medicaments included in the study. Results: MIC of calcium hydroxide and CSNPs against E. faecalis was observed at 2.5 mg/mL and 0.31 mg/mL, respectively. MBC of calcium hydroxide and CSNPs was observed at 2.5 mg/mL and 0.31 mg/mL, respectively. Using Crystal Violet (CV) assay, calcium hydroxide and CSNPs showed biofilm inhibition at concentrations of 2.5 mg/mL and 0.625 mg/mL, respectively. Confocal laser scanning microscopy analysis found that both calcium hydroxide and CSNPs showed a significant decrease in viable cells at their MBC values compared to the control group’s normal saline. CSNPs showed a significantly lower percentage of live cells than calcium hydroxide ( P < 0.05). Conclusion: The study results reveal that the antimicrobial efficacy of CSNPs is better than calcium hydroxide and normal saline against E. faecalis biofilm.