This study systematically evaluated the in vitro antimicrobial activity of the novel quinolone antibiotic delafloxacin against clinically isolated Corynebacterium strains, finding it to have higher sensitivity compared to other quinolone antibiotics. The research also revealed the complexity of resistance mechanisms by analyzing mutations in the quinolone resistance-determining region (QRDR) of the gyrA gene, providing important reference for treatment strategies of Corynebacterium infections.
Literature Overview
This paper, 'In Vitro Activity of Delafloxacin Against Corynebacterium spp.', published in the journal Antibiotics, reviews and summarizes the in vitro antimicrobial activity of delafloxacin and other quinolone antibiotics against clinical isolates of Corynebacterium spp. It also analyzes mutations in resistance-related genes and their impact on minimum inhibitory concentration (MIC). The study demonstrates that delafloxacin exhibits the strongest antimicrobial activity among all tested quinolones, offering a potential new treatment option for Corynebacterium infections.
Background Knowledge
Corynebacterium spp. are opportunistic pathogens commonly found on human skin and mucous membranes, and their clinical significance as agents of nosocomial and device-associated infections has increased in recent years. Resistance to antibiotics, particularly quinolones, is rising, making them a growing challenge in treatment. Mutations in the quinolone resistance-determining region (QRDR) of the DNA gyrase (gyrA) gene are a primary mechanism of resistance. This study compares the antimicrobial activity of delafloxacin and other quinolone antibiotics using standardized broth microdilution (BMD) and gradient strip (Etest) methods, while also analyzing the impact of QRDR mutations on MIC values, aiming to assess the potential of delafloxacin as an alternative treatment and the reliability of in vitro testing.
Research Methods and Experiments
The research team evaluated 53 clinical isolates of Corynebacterium spp., including C. amycolatum (13 isolates), C. glucuronolyticum (10 isolates), C. jeikeium (10 isolates), C. striatum (10 isolates), and C. urealyticum (10 isolates). The MIC values of delafloxacin, ciprofloxacin, levofloxacin, and moxifloxacin were determined using the broth microdilution (BMD) and gradient strip (Etest) methods. In selected experiments, efflux pump inhibitors (reserpine or phenylalanine-arginine-β-naphthylamide) were added to evaluate the impact of efflux mechanisms on resistance. The QRDR region of the gyrA gene was amplified by PCR and sequenced, with mutations identified by alignment to reference genome sequences of each species.
Key Conclusions and Perspectives
Research Significance and Prospects
This study is the first to systematically compare the in vitro antimicrobial activity of the novel quinolone delafloxacin with traditional quinolones against Corynebacterium spp., providing important insights for clinical treatment. Future studies should explore the efficacy of delafloxacin in vivo models and its clinical application potential for treating Corynebacterium infections. Additionally, further investigation into the resistance mechanisms associated with gyrA mutations, using transcriptomic and proteomic approaches, may reveal additional resistance-related pathways.
Conclusion
In summary, this study demonstrates that delafloxacin exhibits superior in vitro antimicrobial activity against Corynebacterium spp. compared to ciprofloxacin, levofloxacin, and moxifloxacin. Delafloxacin MIC values were found to be positively correlated with the number of mutations in the QRDR of the gyrA gene. Gradient strip testing showed good consistency with broth microdilution for determining delafloxacin MICs, supporting its use as an alternative testing method in clinical microbiology laboratories. While no significant role for efflux pumps in quinolone resistance was observed, the variability in MIC values among strains with identical mutation profiles suggests the presence of as-yet-unidentified resistance mechanisms. This study provides valuable data for understanding the molecular basis of quinolone resistance in Corynebacterium spp. and the clinical application of novel antibiotics. Further in vivo and clinical studies are needed to validate its therapeutic potential.
