In vitro activity of gepotidacin and comparator antimicrobials against isolates of nontuberculous mycobacteria (NTM).

Novel antimicrobials are needed to treat rising nontuberculous mycobacteria (NTM) infections. Using standard broth microdilution methods, 68 NTM isolates were tested against gepotidacin, a new, first-in-class, oral triazaacenaphthylene bacterial topoisomerase inhibitor. MICs varied (0.25 to >64 µg/mL) with the lowest being M. fortuitum complex (0.25-8 µg/mL), M. mucogenicum complex (1-2 µg/mL), M. kansasii (0.25-8 µg/mL), and M. marinum (4-16 µg/mL). Testing greater numbers of some species is suggested to better understand gepotidacin activity against NTM.

In vitro activity of gepotidacin against urine isolates of Escherichia coli from outpatient departments in Germany.

BACKGROUND: Escherichia coli is the leading pathogen of community-acquired urinary tract infections. Gepotidacin is a novel, bactericidal, first-in-class triazaacenaphthylene oral antibiotic that inhibits bacterial DNA replication by a distinct mechanism of action that confers activity against most strains of target pathogens, such as E. coli, Staphylococcus saprophyticus and Neisseria gonorrhoeae, including those resistant to other antibiotics. OBJECTIVES: This study assessed the in vitro activity of gepotidacin in comparison with ciprofloxacin and other oral standard-of-care antibiotics using a large collection of urine isolates of E. coli obtained from outpatients in Germany. METHODS: Four hundred and sixty E. coli collected from 23 laboratories during a surveillance study in 2019/2020 were tested. Forty-six isolates (10.0%) produced an ESBL of the CTX-M family, half of which belonged to MDR clonal subgroups of E. coli ST131. Antibiotic susceptibilities were tested at a reference laboratory by broth microdilution according to the standard ISO 20776-1. RESULTS: Fifty-three (11.5%) isolates were ciprofloxacin resistant, 25 (47.2%) of which also produced an ESBL. Overall, MIC50/90 values for gepotidacin were 2/4 mg/L (MIC range 0.125-16 mg/L), with no differences in activity between ciprofloxacin-susceptible and ciprofloxacin-resistant isolates, ESBL-producing and non-ESBL isolates, O25b-ST131 isolates, and isolates susceptible or resistant to fosfomycin, mecillinam or nitrofurantoin. CONCLUSIONS: Gepotidacin showed promising in vitro activity against urine isolates of E. coli, including ciprofloxacin-resistant isolates, ESBL-producing isolates and isolates resistant to oral standard-of-care antibiotics.

Augmented antibacterial activity of ampicillin with silver nanoparticles against methicillin-resistant Staphylococcus aureus (MRSA).

At present, including failed attempts, it takes about 15 years and costs totaling up to $2.6 billion to take a promising new compound from laboratory to the market. Increasing drug resistance among microbial pathogens has led to a growing interest in exploring novel methods to enhance the efficacy of existing drugs. Combination therapies involving two or more known antimicrobial methods, particularly those involving nanoparticles for combating the clinical problems associated with antibiotic resistance, have been garnering interest. In the current study, we determined whether a combination therapy involving silver nanoparticles, which are known for their antimicrobial activity, and the widely used antibiotic ampicillin can be effective against methicillin-resistant Staphylococcus aureus (MRSA). In the presence of sub-lethal dose of silver nanoparticles, ampicillin was found to be effective against MRSA. Indeed, the results show that silver nanoparticles and ampicillin act synergistically, with the effect being more pronounced when a lower concentration of ampicillin is present. When present at a higher concentration, ampicillin coats the silver nanoparticle, preventing the direct interaction of nanoparticles and bacteria. This study discusses the possible applications of combination antimicrobial therapies involving silver nanoparticles for therapeutic treatments.