Abstract
BackgroundGeneration of extended- spectrum β- lactamases is one of the major mechanisms by which clinical Klebsiella pneumoniae develop resistance to antibiotics. Combined antibiotics prove to be a relatively effective method of controlling such resistant strains. Some of Chinese herbal active ingredients are known to have synergistic antibacterial effects. This study is aimed to investigate synergistic effects of Chinese herbal active ingredients with cefotaxime on the extended- spectrum β- lactamase positive strains of Klebsiella pneumoniae, and to analyze mechanism of synergistic action, providing experimental evidence for clinical application of antimicrobial drugs.ResultsFor total sixteen strains including fifteen strains of cefotaxime resistant K. pneumoniae and one extended- spectrum β- lactamase positive standard strain, the synergy rates of cefotaxime with baicalein, matrine, and clavulanic acid were 56.3 %, 0 %, and 100 %, respectively. The fractional inhibitory concentration index of combined baicalein and cefotaxime was correlated with the percentage decrease of cefotaxime MIC of all the strains (r = −0.78, p <0.01). In the group of synergy baicalein and cefotaxime, the transcribed mRNA level of CTX-M-1 after treatment of baicalein was decreased significantly (p <0.05). Moreover, the CTX-M-1 mRNA expression percentage inhibition (100 %, 5/5) was significantly higher than non- synergy group (25 %, 1/4) (p <0.05).ConclusionsOur study demonstrated that baicalein exhibited synergistic activity when combined with cefotaxime against some of extended- spectrum β- lactamases positive K. pneumoniae strains by inhibiting CTX-M-1 mRNA expression. However, no direct bactericidal or bacteriostatic activity was involved in the synergistic action. Baicalein seems to be a promising novel effective synergistic antimicrobial agent.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-016-0797-1) contains supplementary material, which is available to authorized users.
Highlights
Generation of extended- spectrum β- lactamases is one of the major mechanisms by which clinical Klebsiella pneumoniae develop resistance to antibiotics
The aim of the present study was to investigate antibacterial effects of baicalein in association with cefotaxime against extended- spectrum β- lactamase (ESBL) positive K. pneumoniae compared with another candidate Chinese herbal ingredient named matrine, which is a kind of alkaloids containing lactam ring structure from the Sophora genus
Baicalein was dissolved in dimethyl sulfoxide (DMSO) whose final concentration was less than 1 % according to the Clinical and Laboratory Standards Institute (CLSI, USA)
Summary
Generation of extended- spectrum β- lactamases is one of the major mechanisms by which clinical Klebsiella pneumoniae develop resistance to antibiotics. This study is aimed to investigate synergistic effects of Chinese herbal active ingredients with cefotaxime on the extended- spectrum β- lactamase positive strains of Klebsiella pneumoniae, and to analyze mechanism of synergistic action, providing experimental evidence for clinical application of antimicrobial drugs. Extended- spectrum β- lactamases (ESBLs) have the ability of hydrolyzing a variety of antibiotics, such as penicillin, cephalosporins, and monobactams. It is the main mechanism for the formation of various kinds of bacterial resistance. Several studies show that certain active ingredients of Chinese herbs have synergistic inhibitory effects on bacteria with antibiotics, such as baicalein and matrine [2, 3]. Chan et al reported synergistic effects of baicalein with ciprofloxacin against NorA over-expressed methicillin-resistant MRSA [6]
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