Abstract
BACKGROUND: Heteroresistance represents a significant pathway through which sensitive bacteria evolve into resistant strains, posing challenges for current clinical laboratory detection methods. OBJECTIVES: This study aimed to investigate the differences in resistance among K. pneumoniae isolates from various sources, assess the prevalence of chloramphenicol heteroresistance (CHR), and explore the potential causes and key genes associated with CHR. METHODS: K. pneumoniae was isolated from 801 samples obtained from various sources, and its susceptibility to antibacterial agents was assessed. The modified Kirby-Bauer disk diffusion method, population analysis profiling (PAP), and bactericidal curve assays were employed to identify heteroresistant bacteria. Additionally, the growth curve and stability of CHR strains were measured. To analyze the factors influencing the formation of CHR, we detected the resistance genes cmlA, cat1, and floR across 17 resistant subpopulations, along with virulence genes such as fimH, wabG, kfu, uge, and aerobactin. RESULTS: Among the 198 K. pneumoniae tested, resistance rates to nitrofurantoin, tetracycline, and chloramphenicol were found to be 73.74%, 57.58%, and 51.01%, respectively. The prevalence of CHR was determined to be 8.59% (17 out of 198), which significantly diminished the in vitro bactericidal efficacy of chloramphenicol. Notably, 76.47% (13/17) of the isolates harbored the cat1 and/or floR genes, while the prevalence of the virulence genes wabG, fimH, uge, and kfu was 100%, 100%, 76.47%, and 47.06%, respectively. CONCLUSION: The floR and/or cat1 genes are pivotal in the mechanism underlying heteroresistance to chloramphenicol, and the presence of virulence genes could further contribute to the development of CHR.