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. By analyzing mutations in the quinolone resistance-determining regions (QRDR) of the gyrA gene, the research revealed the complexity of resistance mechanisms and provided important reference for treatment strategies against Corynebacterium infections.
Literature Overview
This study, titled '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 clinically isolated Corynebacterium strains, while also analyzing mutations in resistance-related genes and their impact on minimum inhibitory concentrations (MICs). The findings indicate that delafloxacin demonstrates the strongest antimicrobial activity against all tested strains, offering a potential new treatment option for Corynebacterium infections.
Background Knowledge
Corynebacterium spp. are conditionally pathogenic bacteria commonly found on human skin and mucous membranes, and their clinical significance as opportunistic pathogens has been increasing in recent years. Antibiotic resistance, particularly to quinolones, has been rising among these organisms, posing a significant challenge to treatment. Mutations in the quinolone resistance-determining regions (QRDR) of the DNA gyrase (gyrA) gene are a primary mechanism of resistance. This study compared the antimicrobial activity of delafloxacin and other quinolones using standardized broth microdilution (BMD) and gradient strip (Etest) methods, while also analyzing the impact of QRDR mutations on MIC values, aiming to assess delafloxacin's potential as an alternative treatment and the reliability of in vitro testing methods.
Research Methods and Experiments
The research team evaluated 53 clinical isolates of Corynebacterium spp., including C. amycolatum (13 strains), C. glucuronolyticum (10 strains), C. jeikeium (10 strains), C. striatum (10 strains), and C. urealyticum (10 strains). The MIC values of delafloxacin, ciprofloxacin, levofloxacin, and moxifloxacin were determined using broth microdilution (BMD) and gradient strip (Etest) methods. In some experiments, efflux pump inhibitors (reserpine or phenylalanine-arginine-β-naphthylamide) were included to evaluate the impact of efflux mechanisms on drug resistance. The QRDR region of the gyrA gene was amplified and sequenced via PCR, and compared to reference genome sequences of each species to identify mutation types.
Key Conclusions and Perspectives
Research Significance and Prospects
This study represents the first systematic comparison of the in vitro antimicrobial activity of the new quinolone antibiotic delafloxacin with traditional quinolones against Corynebacterium spp., providing valuable data for clinical treatment. Future studies could further explore the in vivo efficacy of delafloxacin and its potential for clinical application in treating Corynebacterium infections. Additionally, investigations combining transcriptomic and proteomic analyses could reveal additional resistance-related pathways linked to gyrA mutations.
Conclusion
In summary, this study demonstrates that delafloxacin exhibits superior in vitro antimicrobial activity against Corynebacterium strains compared to ciprofloxacin, levofloxacin, and moxifloxacin. The MIC values of delafloxacin were found to correlate positively with the number of mutations in the QRDR region of the gyrA gene. Gradient strip testing showed strong consistency with broth microdilution in measuring delafloxacin MICs, supporting its use as an alternative method in clinical microbiology laboratories. While no significant role of efflux pumps in quinolone resistance was identified, the observed MIC variations among strains with identical mutations suggest the possible existence of novel resistance mechanisms. This research provides important data supporting both the molecular basis of quinolone resistance in Corynebacterium and the clinical application potential of delafloxacin, with further in vivo and clinical studies warranted to validate its therapeutic value.
