Page 56
Notes:
Clinical Microbiology: Open Access | ISSN: 2327-5073 | Volume: 7
Microbiology: Education, R&D and Market
7
th
Annual Summit on
September 28-29, 2018 | San Antonio, USA
In vitro
induction of bacterial resistance to Ceftazidime-avibactam and investigation of the resistance
mechanisms
Yosra Modafer, Fur-Chi Chen
and
Xiaofei
Tennessee State University, USA
C
eftazidime-avibactam antibiotic agent is a compound of third-generation cephalosporin ceftazidime and a
novel non-β-lactam β-lactamase inhibitor avibactam. Avibactam was approved for use in the United States
in 2015. It is an active inhibitor of class A, class C, and some class D enzymes. A few clinical studies have been
conducted to study the overall effect of avibactam against carbapenem-resistant Enterobacteriaceae (CRE) that
produce
Klebsiella
pneumoniae carbapenemase (KPC). To date, no studies on the antimicrobial activity of the
combination against Salmonella species have been published. In this study, we looked at the impact of adding
avibactam to ceftazidime to treat ceftazidime-resistance
Salmonella. Senftenberg
(that produce TEM and or OXA).
The primary goal of this examination was to determine if ceftazidime-avibactam can induce resistance in bacteria
after long-term exposure to the combination. We employed a selection method of the combination and avibactam
alone for
S. Senftenberg
. We monitored bacterial resistance, characterized the stability and cross-resistance. The
combination was very effective against the
S. Senftenberg
, the addition of avibactam resulted in a significant
increase in ceftazidime activity, with MICs generally reduced from 512 to 4 μg/ml. S. Seftenberg evolved resistance
to the combination and to avibactam alone under long-term selection pressure with continuously increasing
concentrations of drugs. Cross-resistance of the induced strains to other antimicrobial agents (ampicillin and
ciprofloxacin) was observed. Our results indicated that resistance to the combination could be formed at 5-fold
(higher than 1/2 the MIC). Highly resistant bacteria at 10-fold was isolated for further analysis. Our undergoing
aim is to investigate the potential role of beta-lactamase and other enzymes in resistance mechanism using RNA
sequencing. Most importantly, our preliminary results raise serious attention concerning the long-term risks
correlated with the development and clinical use of ceftazidime-avibactam.
Biography
Yosra Modafer is a PhD student at Tennessee State University. She has her expertise in studying resistance mechanisms to the antibiotic. She also has her master
research in investigating the effect of Miswak (which is a natural wood stick has been used many years ago in Asia and Africa to clean oral teeth and believed to
have antimicrobial activity) on the oral microbes using saliva samples from 18 volunteers (in 2015).
sinyorh87@hotmail.comYosra Modafer et al., Clin Microbiol 2018, Volume: 7
DOI: 10.4172/2327-5073-C3-040