Low-Frequency Ultrasound Enhances Bactericidal Activity of Antimicrobial Agents against Klebsiella pneumoniae Biofilm

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.

Synergistic antibacterial and antibiofilm effects of ultrasound and MEL-A against methicillin-resistant Staphylococcus aureus

“…Ultrasound treatment was employed after biofilm matured and realized by ultrasonic cleaner [23] . The MRSA biofilm formed as described in 2.3.1 and the cultures were refreshed with LB broth containing different concentrations of MEL-A (256, 128, 64 and 32 μg/mL) after 24 h. Then, these microplates were incubated at 37 °C for another 24 h. Finally, the microplates were taken out and immersed in a sterile water-filled ultrasonic bath (JP-040S, Shenzhen, China).…”

Understanding the physical and biological effects of ultrasound on Pseudomonas aeruginosa biofilms

“…The findings were consistent with low frequency ultrasound studies where, multiple exposures reduced the CFU more easily than a single exposure [326,327].…”

“…Multiple ultrasound treatments have been mainly used in in vivo systems where delivering the antibiotics/antimicrobials was the primary objective [166,169,170]. Most recently, successive low frequency ultrasound exposure (5 min, every 8 hours) on in vitro catheter disk populated with S. aureus or Klebsiella pneumoniae strains showed a decrease in the CFU relative to single exposure but, portions of viable biofilm still remained [326,327].…”

Different Aspects of Using Ultrasound to Combat Microorganisms

“…[57] A recent work published by this group addresses combating the highly resistant Klebsiella pneumoniae biofilm. [58] When combined with LFU, the antibiotics meropenem, tigecycline, and fosfomycin significantly reduced the number of bacteria in these biofilms. [58] Cai et al [1] present and summarize the in vitro and in vivo studies on the effect of antibiotics in combination with sonication on microbial biofilms, including reaching three important conclusions.…”

“…[58] When combined with LFU, the antibiotics meropenem, tigecycline, and fosfomycin significantly reduced the number of bacteria in these biofilms. [58] Cai et al [1] present and summarize the in vitro and in vivo studies on the effect of antibiotics in combination with sonication on microbial biofilms, including reaching three important conclusions. First, it was confirmed that the impact of LFU is more potent in reducing bacteria viability in the biofilm than high-frequency ultrasound.…”