Synergistic antibacterial effects of three natural products combined with antibiotics on Klebsiella pneumoniae

Abstract:

This study screened out the natural products that have synergistic antibacterial effects on strain Klebsiella pneumoniae when combined with antibiotics. The K-B method was used to determine the drug resistance of strain K. pneumoniae to eight types of antibiotics. The broth dilution method was used to determine minimal inhibitory concentrations (MICs) of antibiotics and three types of natural products. Checkerboard method was used to determine the synergistic antibacterial activities of antibiotics in combination with anthocyanins or caffeic acid against strain K. pneumoniae. The synergistic bacteriostatic effect of the combination of caffeic acid (CA) and antibiotics was evaluated by time-dependent killing curve. The results showed that: The strain K. pneumoniae was resistant to eight types of antibiotics, and completely resistant to sulfamethoxazole (SMZ), clindamycin, chloramphenicol (CHL) and tetracycline; The MICs of antibiotics ranged from 16 μg/mL to >512 μg/mL; The MICs of anthocyanins and CA were 25 μg/mL and 1 875 μg/mL respectively, which exhibited great antibacterial activities on strain K. pneumoniae, and the MIC of cinnamaldehyde was >250 μg/mL, which had no antibacterial effect against strain K. pneumoniae, and anthocyanins enhanced the susceptibility of strain K. pneumoniae to ceftazidime and CHL by reducing 4-fold of the MICs of two antibiotics; CA synergistically enhanced strain K. pneumoniae susceptibility to 8 kinds of antibiotics, and the MICs of antibiotics decreased by 8~>4 096 times; It is obvious that the synergistic effect of the combination of caffeic acid with antibiotics is better than that of anthocyanins in combination with antibiotics, and furthermore, CA in combination with SMZ or CHL could inhibit bacteria for at least 24 h. This study for the first time reported that the combination of CA with antibiotics had a significant synergistic antibacterial effect on multidrug resistant strain K. pneumoniae, and showed that combination therapy was an effective strategy to reduce the drug resistance of pathogens.