title: Low-Frequency Ultrasound Enhances Antimicrobial Activity of Colistin-Vancomycin Combination against Pan-Resistant Biofilm of Acinetobacter baumannii.
abstract: Acinetobacter baumannii biofilms in catheters are very difficult to treat. Low-frequency ultrasound (LFU) may improve bactericidal or bacteriostatic activity. However, no previous studies have been reported on its efficacy against pan-resistant biofilms of A. baumannii. This study was designed to investigate whether LFU can enhance the activity of colistin, vancomycin and colistin-vancomycin combinations against pan-resistant biofilms of A. baumannii. The efficacy of colistin combinations was determined using the fractional inhibitory concentration index (FICI). The antibacterial effect was determined from bacteria counts in biofilms and the establishment of 24-h time-kill curves. A significantly synergistic effect was detected between colistin and vancomycin (FICI <0.05). We found that although application of LFU (40 kHz, 600 mW/cm(2), 30 min, duty cycle 1:9) alone or in combination with a single agent failed to significantly reduce bacteria counts in biofilms, it apparently enhanced the antibacterial effectiveness of combinations of these agents. Moreover, higher concentrations of colistin in the combination treatments resulted in a better ultrasound-enhanced antibacterial effect. In 24-h time-kill curves, the combination of colistin (8 μg/mL) plus vancomycin (4 μg/mL) with LFU caused a significant reduction in bacteria counts in biofilms after 8 h and a continuing decline until 24 h. Bacterial counts were reduced by 3.77 log(CFU/mL) by LFU plus combinations, compared with combinations without LFU at 24 h. Our results indicate that LFU in combination with colistin plus vancomycin may be useful in treating pan-resistant A. baumannii infections.
authors.affiliation: Department of Clinical Pharmacology, PLA General Hospital, Beijing, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Traditional Chinese Medicine Pharmacy, PLA General Hospital, Beijing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yin
authors.affiliation: Chiamery Medical Sciences Institute of Beijing, Beijing, China.
authors.forename: Chun-Xiao
authors.initials: CX
authors.lastname: Weng
authors.affiliation: Center of Medicine Clinical Research, Translational Medical Center, PLA General Hospital, Beijing, China. Electronic address: caicai_hh@sina.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Cai
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects; D003091:Colistin / Q000494:pharmacology*; D004338:Drug Combinations; D050296:Microbial Viability / Q000187:drug effects; D000069453:Ultrasonic Waves; D014640:Vancomycin / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D014640:Vancomycin; D003091:Colistin
keywords: Biofilm; Colistin; Low-frequency ultrasound; Vancomycin