Silver nanoparticles synthesized with Eucalyptus critriodora ethanol leaf extract stimulate antibacterial activity against clinically multidrug-resistant Acinetobacter baumannii isolated from pneumonia patients

2019 ◽  
Vol 126 ◽  
pp. 245-257 ◽  
Author(s):  
Phitchayapak Wintachai ◽  
Supakit Paosen ◽  
Chutha Takahashi Yupanqui ◽  
Supayang Piyawan Voravuthikunchai
2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S662-S662
Author(s):  
Alita Miller ◽  
Sarah McLeod ◽  
Samir Moussa ◽  
Meredith Hackel

Abstract Background The incidence of infections caused by multidrug-resistant (MDR) Acinetobacter baumannii (Ab) is increasing at an alarming rate in certain regions of the world, including the Middle East. Sulbactam (SUL) has intrinsic antibacterial activity against Ab; however, the prevalence of β-lactamases in Ab has limited its therapeutic utility. Durlobactam (DUR, formerly ETX2514) is a diazabicyclooctenone β-lactamase inhibitor with broad-spectrum activity against Ambler class A, C and D β-lactamases that restores SUL activity in vitro against MDR Ab. SUL-DUR is an antibiotic designed to treat serious infections caused by Acinetobacter, including multidrug-resistant strains, that is currently in Phase 3 clinical development. In global surveillance studies of >3600 isolates from 2012-2017, the MIC90 of SUL-DUR was 2 mg/L. Although surveillance systems to monitor MDR infections in the Middle East are currently being established, quantitative, prevalence-based data are not yet available. Therefore, the potency of SUL-DUR was determined against 190 recent, diverse Ab clinical isolates from this region. Methods 190 Ab isolates were collected between 2016 - 2018 from medical centers located in Israel (N = 47), Jordan (N = 36), Qatar (N = 13), Kuwait (N = 42), Lebanon (N = 8), Saudi Arabia (N = 24) and United Arab Emirates (N = 20). Seventy-five percent and 20.5% of these isolates were from respiratory and blood stream infections, respectively. Susceptibility to SUL-DUR and comparator agents was performed according to CLSI guidelines, and data analysis was performed using CLSI and EUCAST breakpoint criteria where available. Results This collection of isolates was 86% carbapenem-resistant and 90% sulbactam-resistant (based on a breakpoint of 4 mg/L). The addition of SUL-DUR (fixed at 4 mg/L) decreased the sulbactam MIC90 from 64 mg/L to 4 mg/L. Only 3 isolates (1.6%) had SUL-DUR MIC values of > 4 mg/L. This potency was consistent across countries, sources of infection and subsets of resistance phenotypes. Conclusion SUL-DUR demonstrated potent antibacterial activity against recent clinical isolates of Ab from the Middle East, including MDR isolates. These data support the global development of SUL-DUR for the treatment of MDR Ab infections. Disclosures Alita Miller, PhD, Entasis Therapeutics (Employee) Sarah McLeod, PhD, Entasis Therapeutics (Employee) Samir Moussa, PhD, Entasis Therapeutics (Employee)


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Helal F. Hetta ◽  
Israa M. S. Al-Kadmy ◽  
Saba Saadoon Khazaal ◽  
Suhad Abbas ◽  
Ahmed Suhail ◽  
...  

AbstractWe aimed to isolate Acinetobacter baumannii (A. baumannii) from wound infections, determine their resistance and virulence profile, and assess the impact of Silver nanoparticles (AgNPs) on the bacterial growth, virulence and biofilm-related gene expression. AgNPs were synthesized and characterized using TEM, XRD and FTIR spectroscopy. A. baumannii (n = 200) were isolated and identified. Resistance pattern was determined and virulence genes (afa/draBC, cnf1, cnf2, csgA, cvaC, fimH, fyuA, ibeA, iutA, kpsMT II, PAI, papC, PapG II, III, sfa/focDE and traT) were screened using PCR. Biofilm formation was evaluated using Microtiter plate method. Then, the antimicrobial activity of AgNPs was evaluated by the well-diffusion method, growth kinetics and MIC determination. Inhibition of biofilm formation and the ability to disperse biofilms in exposure to AgNPs were evaluated. The effect of AgNPs on the expression of virulence and biofilm-related genes (bap, OmpA, abaI, csuA/B, A1S_2091, A1S_1510, A1S_0690, A1S_0114) were estimated using QRT-PCR. In vitro infection model for analyzing the antibacterial activity of AgNPs was done using a co-culture infection model of A. baumannii with human fibroblast skin cell line HFF-1 or Vero cell lines. A. baumannii had high level of resistance to antibiotics. Most of the isolates harbored the fimH, afa/draBC, cnf1, csgA and cnf2, and the majority of A. baumannii produced strong biofilms. AgNPs inhibited the growth of A. baumannii efficiently with MIC ranging from 4 to 25 µg/ml. A. baumannii showed a reduced growth rate in the presence of AgNPs. The inhibitory activity and the anti-biofilm activity of AgNPs were more pronounced against the weak biofilm producers. Moreover, AgNPs decreased the expression of kpsMII , afa/draBC,bap, OmpA, and csuA/B genes. The in vitro infection model revealed a significant antibacterial activity of AgNPs against extracellular and intracellular A. baumannii. AgNPs highly interrupted bacterial multiplication and biofilm formation. AgNPs downregulated the transcription level of important virulence and biofilm-related genes. Our findings provide an additional step towards understanding the mechanisms by which sliver nanoparticles interfere with the microbial spread and persistence.


Author(s):  
Joy James Costa ◽  
Hassan Hosseinzadeh ◽  
Dabasish Kumar Saha ◽  
Shihab Uddin Al Mahmud ◽  
Bhuiyan Mohammad Mahtab Uddin ◽  
...  

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