Abstract
Klebsiella pneumoniae biofilms on inserted devices have been proposed as one of the important factors for hospital-acquired infections, which cause increased resistance to currently used antibiotics. Therefore, it is urgently necessary to develop new treatments with more efficient bacterial clearance. In the present study, we aimed at investigating whether low-frequency ultrasound (LFU) could enhance the bactericidal activity of antimicrobial agents (meropenem (MEM), tigecycline (TGC), fosfomycin (FOM), amikacin (AMK), and colistin (COL)) against K. pneumoniae biofilm infection. K. pneumoniae biofilm was cultivated on the catheter in vitro. Synergistic effects were observed in groups of single ultrasound (S-LFU, 5 min) or multiple ultrasound (M-LFU, 5 min every 8 h (q8h)) in combination with MEM, TGC, and FOM. However, AMK and COL did not show the synergistic effect with either S-LFU or M-LFU. S-LFU in combination with FOM only significantly decreased bacterial counts right after ultrasound, while M-LFU could prolong the synergistic effect until 24 h. The results showed that LFU in combination with antimicrobial agents had a synergistic effect on K. pneumoniae biofilm, and M-LFU might extend the time of synergistic effect compared with S-LFU.
Highlights
Bacterial counts were significantly decreased in S-low-frequency ultrasound (LFU) plus MEM, TGC, FOM, or AMK groups compared with the individual drug groups, while the synergistic effect was retained until 24 h only in the S-LFU plus MEM or TGC group
At 24 h, viable bacterial counts were significantly decreased in all groups compared with the control group, except for AMK and S-LFU alone groups
Similar to S-LFU plus antimicrobial agent groups, viable bacterial counts were significantly decreased in all groups compared with the control group, except for the AMK alone group
Summary
According to CLSI guidelines, susceptibility test of five antimicrobial agents was performed by the broth microdilution method [7]. K. pneumoniae strain was incubated on catheter disks (diameter 0.5 cm) in 24-well plates. 2 mL MHB and 100 μL bacterial suspension (1.5 × 108 CFU/mL) were added to each well, followed by incubation at 37°C for 3 days. Ree biofilm disks and 1 mL MHB in the presence of antimicrobial agents were added to each well of a 24-well plate. E biofilm disks were treated with MEM, AMK, TGC, and FOM at 4 × MIC or COL at 4 μg/mL in the absence or presence of LFU [11]. After S-LFU or M-LFU treatment, the 24-well plates were cultivated at 37°C for 24 h.
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