scholarly journals Activity of β-lactam/taniborbactam (VNRX-5133) combinations against carbapenem-resistant Gram-negative bacteria

2020 ◽  
Vol 76 (1) ◽  
pp. 160-170
Author(s):  
Shazad Mushtaq ◽  
Anna Vickers ◽  
Michel Doumith ◽  
Matthew J Ellington ◽  
Neil Woodford ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Stenotrophomonas Maltophilia ◽  
Clinical Development ◽  
Published Data ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Class A ◽  
Carbapenem Resistant ◽  
Elizabethkingia Meningoseptica

Abstract Background Boronates are of growing interest as β-lactamase inhibitors. The only marketed analogue, vaborbactam, principally targets KPC carbapenemases, but taniborbactam (VNRX-5133, Venatorx) has a broader spectrum. Methods MICs of cefepime and meropenem were determined combined with taniborbactam or avibactam for carbapenem-resistant UK isolates. β-Lactamase genes and porin alterations were sought by PCR or sequencing. Results Taniborbactam potentiated partner β-lactams against: (i) Enterobacterales with KPC, other class A, OXA-48-like, VIM and NDM (not IMP) carbapenemases; and (ii) Enterobacterales inferred to have combinations of ESBL or AmpC activity and impermeability. Potentiation of cefepime (the partner for clinical development) by taniborbactam was slightly weaker than by avibactam for Enterobacterales with KPC or OXA-48-like carbapenemases, but MICs of cefepime/taniborbactam were similar to those of ceftazidime/avibactam, and the spectrum was wider. MICs of cefepime/taniborbactam nonetheless remained >8 + 4 mg/L for 22%–32% of NDM-producing Enterobacterales. Correlates of raised cefepime/taniborbactam MICs among these NDM Enterobacterales were a cefepime MIC >128 mg/L, particular STs and, for Escherichia coli only: (i) the particular blaNDM variant (even though published data suggest all variants are inhibited similarly); (ii) inserts in PBP3; and (iii) raised aztreonam/avibactam MICs. Little or no potentiation of cefepime or meropenem was seen for Pseudomonas aeruginosa and Acinetobacter baumannii with MBLs, probably reflecting slower uptake or stronger efflux. Potentiation of cefepime was seen for Stenotrophomonas maltophilia and Elizabethkingia meningoseptica, which have both chromosomal ESBLs and MBLs. Conclusions Taniborbactam broadly reversed cefepime or meropenem non-susceptibility in Enterobacterales and, less reliably, in non-fermenters.

scholarly journals National Surveillance of Antimicrobial Susceptibility of Bacteremic Gram-Negative Bacteria with Emphasis on Community-Acquired Resistant Isolates: Report from the 2019 Surveillance of Multicenter Antimicrobial Resistance in Taiwan (SMART)

2020 ◽  
Vol 64 (10) ◽  
Author(s):  
Po-Yu Liu ◽  
Yu-Lin Lee ◽  
Min-Chi Lu ◽  
Pei-Lan Shao ◽  
Po-Liang Lu ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Resistance ◽  
Klebsiella Pneumoniae ◽  
Gram Negative Bacteria ◽  
National Surveillance ◽  
Gram Negative ◽  
Content Type ◽  
E Coli ◽  
Carbapenem Resistant

ABSTRACT A multicenter collection of bacteremic isolates of Escherichia coli (n = 423), Klebsiella pneumoniae (n = 372), Pseudomonas aeruginosa (n = 300), and Acinetobacter baumannii complex (n = 199) was analyzed for susceptibility. Xpert Carba-R assay and sequencing for mcr genes were performed for carbapenem- or colistin-resistant isolates. Nineteen (67.8%) carbapenem-resistant K. pneumoniae (n = 28) and one (20%) carbapenem-resistant E. coli (n = 5) isolate harbored blaKPC (n = 17), blaOXA-48 (n = 2), and blaVIM (n = 1) genes.

scholarly journals ARGONAUT-I: Activity of Cefiderocol (S-649266), a Siderophore Cephalosporin, against Gram-Negative Bacteria, Including Carbapenem-Resistant Nonfermenters and Enterobacteriaceae with Defined Extended-Spectrum β-Lactamases and Carbapenemases

2018 ◽  
Vol 63 (1) ◽  
Author(s):  
Michael R. Jacobs ◽  
Ayman M. Abdelhamed ◽  
Caryn E. Good ◽  
Daniel D. Rhoads ◽  
Kristine M. Hujer ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Acinetobacter Baumannii ◽  
Stenotrophomonas Maltophilia ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Extended Spectrum ◽  
Mueller Hinton ◽  
Mueller Hinton Broth

ABSTRACT The activity of the siderophore cephalosporin cefiderocol is targeted against carbapenem-resistant Gram-negative bacteria. In this study, the activity of cefiderocol against characterized carbapenem-resistant Acinetobacter baumannii complex, Stenotrophomonas maltophilia, Pseudomonas aeruginosa, and Enterobacteriaceae strains was determined by microdilution in iron-depleted Mueller-Hinton broth. The MIC90s against A. baumannii, S. maltophilia, and P. aeruginosa were 1, 0.25, and 0.5 mg/liter, respectively. Against Enterobacteriaceae, the MIC90 was 1 mg/liter for the group harboring OXA-48-like, 2 mg/liter for the group harboring KPC-3, and 8 mg/liter for the group harboring TEM/SHV ESBL, NDM, and KPC-2.

scholarly journals MexAB-OprM Efflux Pump Interaction with the Peptidoglycan of Escherichia coli and Pseudomonas aeruginosa

2021 ◽  
Vol 22 (10) ◽  
pp. 5328
Author(s):  
Miao Ma ◽  
Margaux Lustig ◽  
Michèle Salem ◽  
Dominique Mengin-Lecreulx ◽  
Gilles Phan ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Cell Division ◽  
Membrane Proteins ◽  
Outer Membrane ◽  
Efflux Pump ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Active Efflux

One of the major families of membrane proteins found in prokaryote genome corresponds to the transporters. Among them, the resistance-nodulation-cell division (RND) transporters are highly studied, as being responsible for one of the most problematic mechanisms used by bacteria to resist to antibiotics, i.e., the active efflux of drugs. In Gram-negative bacteria, these proteins are inserted in the inner membrane and form a tripartite assembly with an outer membrane factor and a periplasmic linker in order to cross the two membranes to expulse molecules outside of the cell. A lot of information has been collected to understand the functional mechanism of these pumps, especially with AcrAB-TolC from Escherichia coli, but one missing piece from all the suggested models is the role of peptidoglycan in the assembly. Here, by pull-down experiments with purified peptidoglycans, we precise the MexAB-OprM interaction with the peptidoglycan from Escherichia coli and Pseudomonas aeruginosa, highlighting a role of the peptidoglycan in stabilizing the MexA-OprM complex and also differences between the two Gram-negative bacteria peptidoglycans.

scholarly journals Emergence of Colistin Resistant Gram-Negative Bacteria in a Tertiary Care Rural Hospital in 2019

KYAMC Journal ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 87-90
Author(s):  
Abdullah Akhtar Ahmed ◽  
Nusrat Akhtar Juyee ◽  
SM Ali Hasan
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Tertiary Care ◽  
Salmonella Typhi ◽  
Rural Hospital ◽  
Gram Negative Bacteria ◽  
Bacterial Isolates ◽  
Colistin Resistance ◽  
Sensitivity Testing ◽  
Gram Negative

Background: Colistin-resistant Gram-negative bacteria is a rapidly emerging global threatgenerated a sense of public alarm. Objective: To combat this challenge a study was designedto evaluate the fast spreading infections by colistin-resistant pathogens in the tertiary care rural hospital of Bangladesh. Materials and Methods: To study isolation ofpathogenic gram-negative bacilli,clinical sample (n-640) of hospitalized patients of Khwaja Yunus Ali Medical College Hospital in Enayetpur, Bangladesh during the 1st quarter of the year 2019 were used. The bacterial isolates were screened for meropenem and colistin-resistance. Results: A total of 156 bacterial isolates were studied which included Escherichia coli (n-112), Klebsiella pneumoniae (n-14), Pseudomonas aeruginosa (n-27), and Salmonella typhi (n-3). Antibiotic sensitivity testing showed that 32/156(20%) and 119/156 (76%) isolates were resistant to meropenem and colistin, respectively. whereas 50/156 (32%) isolates were resistant to both antibiotics. Escherichia coli, K. pneumoniae, pseudomonas aeruginosa, and Salmonella typhi isolates respectivelywere 112/156 (72%), 14/156 (9%). 27/156 (17%), and 3/156 (2%). Conclusion: Colistin is typically used as salvage therapy, or last-line treatment, for MDR gramnegative infections.But there is worrisome therapeutic scenario in our study finding of colistin resistance is 76% in Gram-negative bacteria of the clinical isolates. The restricted and rational use of colistin drug is the need of hour. KYAMC Journal Vol. 11, No.-2, July 2020, Page 87-90

scholarly journals Treatment Options for Carbapenem-resistant Gram-negative Bacterial Infections

2019 ◽  
Vol 69 (Supplement_7) ◽  
pp. S565-S575 ◽  
Author(s):  
Yohei Doi
Keyword(s):  
Bacterial Infections ◽  
Treatment Options ◽  
Clinical Development ◽  
Gram Negative Bacteria ◽  
First Line ◽  
Safe Alternative ◽  
New Agents ◽  
Gram Negative ◽  
Carbapenem Resistant

AbstractAntimicrobial resistance has become one of the greatest threats to public health, with rising resistance to carbapenems being a particular concern due to the lack of effective and safe alternative treatment options. Carbapenem-resistant gram-negative bacteria of clinical relevance include the Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, and more recently, Stenotrophomonas maltophilia. Colistin and tigecycline have been used as first-line agents for the treatment of infections caused by these pathogens; however, there are uncertainties regarding their efficacy even when used in combination with other agents. More recently, several new agents with activity against certain carbapenem-resistant pathogens have been approved for clinical use or are reaching late-stage clinical development. They include ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, plazomicin, eravacycline, and cefiderocol. In addition, fosfomycin has been redeveloped in a new intravenous formulation. Data regarding the clinical efficacy of these new agents specific to infections caused by carbapenem-resistant pathogens are slowly emerging and appear to generally favor newer agents over previous best available therapy. As more treatment options become widely available for carbapenem-resistant gram-negative infections, the role of antimicrobial stewardship will become crucial in ensuring appropriate and rationale use of these new agents.

Susceptibility of Gram-negative bacteria to the synergistic bactericidal action of serum and polymyxin B nonapeptide

1986 ◽  
Vol 32 (1) ◽  
pp. 66-69 ◽  
Author(s):  
Petri Viljanen ◽  
Helena Käyhty ◽  
Martti Vaara ◽  
Timo Vaara
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Enterobacter Cloacae ◽  
Polymyxin B ◽  
Gram Negative Bacteria ◽  
Bactericidal Action ◽  
Gram Negative ◽  
Degree Of Sensitization ◽  
Normal Human ◽  
Klebsiella Spp

Polymyxin B nonapeptide was able to sensitize Escherichia coli strains and strains of Salmonella typhimurium, Klebsiella spp., Enterobacter cloacae, Pseudomonas aeruginosa, and Haemophilus influenzae to the bactericidal action of fresh normal human serum. The degree of sensitization varied significantly within the strains. Strains of Proteus mirabilis, Neisseria gonorrhoeae, and N. meningitidis remained resistant.

scholarly journals Infections in patients colonized with carbapenem-resistant Gram-negative bacteria in a medium Spanish city

2021 ◽  
Author(s):  
Carmen Soria-Segarra ◽  
Mercedes Delgado-Valverde ◽  
María Luisa Serrano-García ◽  
Inmaculada López-Hernández ◽  
José María Navarro-Marí ◽  
...  
Keyword(s):  
Predictive Value ◽  
Stenotrophomonas Maltophilia ◽  
Sanger Sequencing ◽  
Clinical Samples ◽  
Clinical Implications ◽  
Gram Negative Bacteria ◽  
Cross Sectional ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Pulsed Field Electrophoresis

Objective. Because there are few studies on the clinical implications of colonization by carbapenem-resistant gram-negative bacteria (CRB) this was analyzed in rectal smears (RS) and pharyngeals (PS) and its ability to predict infection/colonization. Methodology. A cross-sectional, retrospective study from adult inpatients between January 2016 and December 2019 was conducted. The isolates were characterized by MicroScan and spectrometry of masses applying EUCAST 2018 cutoff points. The detection of carbapenemases was performed by PCR and Sanger sequencing; sequencies was assigned by MLST. The genetic relationship between the clinical isolates was made by pulsed field electrophoresis using the enzymes Xbal, Spel or Apal. Results. A total of 308 (86.03%) RS and 50 (13.97%) positive PS were detected, the RS had a 85% sensibility, 100% specificity, 100% positive predictive value and 97% negative predictive value. In RS, the following were isolated: 44% (n=135) Acinetobacter baumannii, 26% (n =80) Enterobacterales (20 KPC, 29 OXA-48, 22 VIM, 2 IMP, 7 NDM), 17% (n=53) Pseudomonas aeruginosa and 13% (n=40) Stenotrophomonas maltophilia. In the PS were isolated 44% (n=22) S. maltophilia, 40% (n = 20) A. baumannii, 8% (n=4) P. aeruginosa and 8% (n=4) Enterobacterales (3 VIM, 1 OXA). From the patients with simultaneous RS and PS, 41 (40.6%) had positivity in both smears, 45 (44.6%) only in RS and 15 (14.9%) only in PS. Colonization preceded infection in 81.3% (n=13) of the isolates; association between infection and colonization was found (p<0.001; χ2); and the episodes where the information was found all the isolates from the clinical samples and from the smears were similar. Conclusions. The probability of predicting infection through the CRB colonized in different clinical samples is feasible. The RS has a major sensibility to detect colonization.

scholarly journals Gram Negative Bacteria (GNB) Isolated From Used Home-made and Surgical Nose/Face Mask by Local Residents of Akungba Akoko, Ondo State, a Threat to Life and False Sense of Protection against SARS-CoV-2 (COVID-19)

2021 ◽  
pp. 1-17
Author(s):  
Oludare Temitope Osuntokun
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Proteus Mirabilis ◽  
Antimicrobial Agents ◽  
Face Mask ◽  
Gram Negative Bacteria ◽  
Haemophilus Influenza ◽  
Gram Negative ◽  
False Sense ◽  
Zones Of Inhibition

Nose/Face masks are physical barriers to respiratory droplets that may enter through the nose and mouth to cause infections in the respiratory tract. The study was determined and assess the presence of Gram-negative bacteria in used home-made and surgical nose mask by residents of Akungba-Akoko Ondo State and to determine the antimicrobial susceptibility and resistant profile of the isolated bacteria to eight (8) different antimicrobial agents. The antimicrobial analysis were performed using standard microbiological and biochemical methods. Antimicrobial Susceptibility test of all identified isolates to antimicrobial agents were determined using the standard Kirby-Bauer disk diffusion method. The Gram-negative bacteria that were detected from the used home-made and surgical nose mask in this study include: Haemophilus influenza, Proteus mirabilis, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumonia. During this study, all the Gram-negative bacteria isolates were resistant to Ciproflox in both used home-made and surgical nose mask. All isolates were also resistant to Ampicilin, Augmentin, Septrin and Streptomycin. In this study, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa were isolated organism from used home-made nose mask, it was observed that Escherichia coli were resistant to Augmentin, Tarivid, Ciproflox, Gentamycin, and Reflaxine, and Pseudomonas aeruginosa were resistant to Tarivid, Ciproflox, and Nalidixic acid between 20 mm and 24 mm zones of inhibition respectively. Haemophilus influenza, Pseudomonas aeruginosa, Escherichia coli and Proteus mirabilis were isolated organism from used surgical nose mask. It was observed that all isolated organisms from the used surgical nose/face mask were resistant to Augmentin and Gentamycin between 20 and 24 mm zones of inhibition respectively. Klebsiella pneumoniae were isolated from both used home-made and surgical nose/face mask and were found to be resistant to Streptomycin, Septrin, Ampicilin, and Gentamicin between 20 to 22 mm zones of inhibition respectively. Proteus mirabilis were isolated from used surgical nose/face mask,        they were found to be resistant to Ciproflox at 21mm zones of inhibition. Haemophilus influenza were resistant to Ampicilin, Septrin, Streptomycin, and Augmentin at 23 mm zones of inhibition. Isolates from used both home-made and surgical nose/face mask were subjected to modified and synergized antibiotics, it was observed that the isolates from both used home-made and surgical nose mask were resistant to all modified and synergized antibiotics between 20 and 25 mm zones of inhibition respectively. The result of this study validates the potency of  Gram negative bacteria isolated from used both home-made and surgical nose/face mask and the degree of invasion and evasiveness, thereby causing various degrees of infections and a false sense of protection against SARS-CoV-2 (COVID-19). Finding from this research recommends a stringent measures were needed to be implemented, to halt and combat this revenging situation especially in the new era of mutating SARS-CoV-2 Virus not only in Nigeria, worldwide at large.

scholarly journals Green Synthesis of Silver Nanoparticles Using Novel Launaea Procumbens Leaves Extract and Screening Its Antibacterial Activity

2021 ◽  
Author(s):  
Sanjay Ratan Kumavat ◽  
SATYENDRA MISHRA
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Silver Nanoparticles ◽  
Green Synthesis ◽  
Gram Negative Bacteria ◽  
Zone Of Inhibition ◽  
Gram Negative ◽  
Green Synthesized Silver Nanoparticles ◽  
Launaea Procumbens

Abstract Plants are emerging as a cost-effective and ecofriendly method for green synthesis of nanoparticles. The plant extract Launaea procumbens was used as a reduction agent in the green synthesis of silver nanoparticles. UV-Visible spectroscopy, HR-TEM, SAED, FE-SEM, EDAX, DLS, and FT-IR were used to study the green synthesized silver nanoparticles. UV-Vis spectroscopy of a prepared silver solution revealed maximum absorption at 435 nm. The synthesized silver nanoparticles were found to be spherical in shape with a size in the range of 24.28 to 31.54 nm. DLS analysis was used to determine the size of the green synthesized silver nanoparticles, which showed outstanding antibacterial action against Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus, as well as Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa. Gram-positive Bacillus subtilis had a maximum zone of inhibition of 20 mm, Staphylococcus aureus had a zone of inhibition of 19 mm, and Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa had zones of inhibition of 13 mm.

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