Journal of Bacteriology & Parasitology

Antimicrobial peptide novicidin synergises with rifampicin, ceftriaxone and ceftazidime against antibiotic-resistant gram-negative Enterobacteriaceae in vitro

3^rd International Congress on Bacteriology and Infectious Diseases

August 04-06, 2015 Valencia, Spain

Yanmin Hu, OdelSoren, Dipesh Patel, Yingjun Liu, Karoline Sidelmann Brinch, Alexander Liu and Anthony Coates

Scientific Tracks Abstracts: J Bacteriol Parasitol

Abstract:

Infections caused by gram-negative bacteria species such as those in the Enterobactericeae family are responsible for high
rates of morbidity and mortality. The spread of antibiotic resistance amongst gram-negative pathogens is a serious clinical
threat requiring urgent attention. Traditional novel drug development inevitably leads to emergence of new resistant bacterial
strains, rendering the new drugs ineffective. Therefore reviving the therapeutic potentials of existing antibiotics represents
an attractive novel strategy. Novicidin, a novel cationic antimicrobial peptide is effective against gram-negative bacteria. The
actions of novicidin in combination with rifampicin, ceftriaxone and ceftazidime were investigated. We performed in vitro
investigations to test against 94 antibiotic resistant clinical Gram-negative isolates and 7 strains containing New Delhi metallo-
β-lactamase-1 (NDM-1). The effects of combining novicidin with rifampicin, ceftriaxone and ceftazidime were examined
using the chequerboard method and time kill curves. A fluorescence assay was used to investigate the depolarisation of the
bacterial cell membrane by novicidin. The post antibiotic effect was measured. The cytotoxicity and haemolysis of novicidin
were examined using neutral red uptake in the L929 fibroblast cell line and lysis of human blood. Novicidin combined with
rifampicin showed synergy with over 70% of the tested gram-negative clinical isolates (n=94) and NDM-1 strains (n=7)
reducing the MIC significantly. The combination of novicidin with ceftriaxone and ceftazidime showed synergistic effects with
more than 89.7% of ceftriaxone-resistant strains and 94.1% of ceftazidime-resistant strains. These synergistic combinations were
also demonstrated using time kill studies with multiple strains. We also demonstrated that novicidin altered the cytoplasmic
membrane potential by membrane depolarisation against both Escherichia coli and an isolate from the Klebsiella-Enterobacter-
Serratia (KES) group. Furthermore, novicidin was shown to increase the post-antibiotic effect (PAE) when combined with
rifampicin or ceftriaxone. Novicidin showed low haemolytic activity and conservation of cell viability in the cell culture post
treatment. We demonstrated that novicidin strongly rejuvenates the therapeutic potencies of ceftriaxone or ceftazidime against
ceftriaxone or ceftazidime resistant gram-negative bacteria in vitro. In addition, novicidin boosted the activity of rifampicin.
This strategy can have major clinical implications in our fight against antibiotic resistance bacterial infections.

Biography :

Yanmin Hu is a Senior Research Fellow at St George’s, University of London. Her main research interests are in tuberculosis and antibiotic discovery. The scientific
and intellectual imperatives for her research include new drugs and better drug regimen for tuberculosis and other important infectious diseases; improved
chemotherapy to eradicate persistent bacteria; molecular approaches to understand the processes of infection and pathogenesis of M. tuberculosis and other
pathogens.