The role of synonymous mutations in the evolution of TEM β-lactamase genes
Antimicrob Agents Chemother. 2021 Apr 5:AAC.00018-21. doi: 10.1128/AAC.00018-21. Online ahead of print.ABSTRACTNonsynonymous mutations are well documented in TEM β-lactamases. The resulting amino acid changes often alter the conferred phenotype from broad spectrum (2b) conferred by TEM-1 to extended spectrum (2be), inhibitor resistant (2br), or both extended spectrum and inhibitor resistant (2ber). The encoding bla TEM genes also deviate in numerous synonymous mutations, which are not well understood. bla TEM-3 (2be), bla TEM-33 (2br), and bla TEM-109 (2ber) were studied in comparison to bla TEM-1 bla TEM-33 was chose...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Mohammad Faheem Charles J Zhang Monica N Morris Juergen Pleiss Peter Oelschlaeger Source Type: research

Novel Specific Metallo- ß-lactamase Inhibitor, ANT2681, Restores Meropenem Activity to Clinically Effective Levels Against NDM-Positive Enterobacterales
Antimicrob Agents Chemother. 2021 Apr 5:AAC.00203-21. doi: 10.1128/AAC.00203-21. Online ahead of print.ABSTRACTThe global dissemination of metallo-ß-lactamase (MBL)-producing carbapenem resistant Enterobacterales (CRE) is a serious public health concern. Specifically, NDM (New Delhi MBL) has been a major cause of carbapenem therapy failures in recent years, particularly as effective treatments for serine-ß-lactamase (SBL)-producing Enterobacterales are now commercially available. Since the NDM gene is carried on promiscuous plasmids encoding multiple additional resistance determinants, a large proportion of NDM...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Magdalena Zalacain Clarisse Lozano Agustina Llanos Nicolas Sprynski Thomas Valmont Cyntia De Piano David Davies Simon Leiris Carole Sable Adeline Ledoux Ian Morrissey Marc Lemonnier Martin Everett Source Type: research

Identification of a novel ciprofloxacin tolerance gene, < em > aciT, < /em > which contributes to filamentation in < em > Acinetobacter baumannii < /em >
Antimicrob Agents Chemother. 2021 Apr 5:AAC.01400-20. doi: 10.1128/AAC.01400-20. Online ahead of print.ABSTRACTFluoroquinolones are one of the most prescribed broad-spectrum antibiotics. However, their effectiveness is being compromised by high rates of resistance in clinically important organisms including Acinetobacter baumannii We sought to investigate the transcriptomic and proteomic responses of the clinical A. baumannii strain AB5075-UW upon exposure to sub-inhibitory concentrations of ciprofloxacin. Our transcriptomics and proteomics analysis found that the most highly expressed genes and proteins were components of...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Varsha Naidu Bhumika Shah Karthik S Kamath Hsin-Ya Chien Stephanie Nagy Alaska Pokhrel Mark Molloy Karl A Hassan Ian T Paulsen Source Type: research

Dosage individualization of linezolid: precision dosing of linezolid to optimise efficacy and minimise toxicity
Antimicrob Agents Chemother. 2021 Apr 5:AAC.02490-20. doi: 10.1128/AAC.02490-20. Online ahead of print.ABSTRACTHigh interindividual variability in the pharmacokinetics (PK) of linezolid has been described, which results in an unacceptably high proportion of patients with either suboptimal or potentially toxic concentrations following the administration of a fixed regimen. The aim of this study was to develop a population pharmacokinetic model of linezolid and use this to build and validate alogorithms for individualised dosing.A retrospective pharmacokinetic analysis was performed using data from 338 hospitalized patients ...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: S Luque W Hope L Sorli R Mu ñoz-Bermudez N Campillo J Barcel ó F Álvarez-Lerma J P Horcajada J R Masclans-Enviz M Neely S Grau Source Type: research

Azoles susceptibility profiles of more than 9,000 clinical yeast isolates belonging to 40 common and rare species
Antimicrob Agents Chemother. 2021 Apr 5:AAC.02615-20. doi: 10.1128/AAC.02615-20. Online ahead of print.ABSTRACTInvasive yeast infections represent a major global public health issue and only few antifungal agents are available. Azoles are one of the classes of antifungals used for treatment of invasive candidiasis. The determination of antifungal susceptibility profiles using standardized methods is important to identify resistant isolates and to uncover the potential emergence of intrinsically-resistant species. We here report data on 9,319 clinical isolates belonging to 40 pathogenic yeast species recovered in France ove...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Marie Desnos-Ollivier Olivier Lortholary St éphane Bretagne Fran çoise Dromer French Mycoses Study Group Source Type: research

Co-production of Tet(X7) conferring high-level tigecycline resistance, fosfomycin FosA4 and colistin Mcr-1.1 in < em > Escherichia coli < /em > strains from chickens in Egypt
Antimicrob Agents Chemother. 2021 Apr 5:AAC.02084-20. doi: 10.1128/AAC.02084-20. Online ahead of print.ABSTRACTThe plasmid-mediated tet(X7) conferring high-level tigecycline resistance was identified in five mcr-1.1-positive Escherichia coli strains [ST10 (n=3), and ST155 (n=2)] isolated from chickens, Egypt. Two fosfomycin-resistant fosA4-carrying IncFII plasmids (⁓79 kb in size) were detected. Transposase ISCR3 (IS91 family) is syntenic with tet(X7) in all isolates suggesting its role in the mobilization of tet(X7). To our knowledge, this is the first global report of (ST4)-IncHI2 plasmids co-carrying tet(X7) and mcr-1...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Ahmed M Soliman Hazem Ramadan Hoda Zarad Yo Sugawara Liansheng Yu Motoyuki Sugai Toshi Shimamoto Lari M Hiott Jonathan G Frye Charlene R Jackson Tadashi Shimamoto Source Type: research

< em > Physiological responses of < /em > < em > Aspergillus niger < /em > < em > challenged with itraconazole < /em >
Antimicrob Agents Chemother. 2021 Apr 5:AAC.02549-20. doi: 10.1128/AAC.02549-20. Online ahead of print.ABSTRACTAspergillus niger is an opportunistic pathogen commonly found in a variety of indoor and outdoor environments. An environmental isolate of A. niger from a pig farm were resistant to itraconazole and in-depth investigations were conducted to better understand cellular responses during growth when exposed to an antifungal.Using a combination of cultivation techniques, antibiotic stress-testing, and label-free proteomics, this study has investigated the physiological and metabolic responses of A. niger to sublethal l...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Jan Struckmann Poulsen Anne Mette Madsen John Kerr White Jeppe Lund Nielsen Source Type: research

Distinguishing < em > bla < /em > < sub > KPC < /sub > -gene-containing IncF plasmids from epidemiologically related and unrelated Enterobacteriaceae based on short- and long-read sequence data
This study aimed to evaluate the performance of three approaches to distinguish epidemiologically related from unrelated bla KPC-containing pKpQiL-like IncFII(k2)-IncFIB(pQiL) plasmids.METHOD: Epidemiologically related isolates, were short- and long-read whole genome sequenced. A hybrid assembly was performed and plasmid sequences were extracted from the assembly graph. Epidemiologically unrelated plasmid sequences were extracted from the GenBank. Pairwise comparisons were performed of epidemiologically related and unrelated plasmids based on SNP differences using snippy, phylogenetic distance using Roary and using a simil...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Joep J J M Stohr Marjolein F Q Kluytmans-van den Bergh Veronica A T C Weterings John W A Rossen Jan A J W Kluytmans Source Type: research

Vitamin E and K < sub > 1 < /sub > as anti-quorum sensing agents against < em > Pseudomonas aeruginosa < /em > : A new insight
Antimicrob Agents Chemother. 2021 Apr 5:AAC.01342-20. doi: 10.1128/AAC.01342-20. Online ahead of print.ABSTRACTToday, anti-virulence compounds which attenuate bacterial pathogenicity and have no interference with bacterial viability or growth are introduced as next generation of antibacterial agents. However, the development of such compounds that can be used by humans is restricted by various factors, including the need for extensive economic investments, the inability of many molecules to penetrate the membrane of Gram-negative bacteria, or unfavorable pharmacological properties and cytotoxicity.Here, we take a new and d...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Sadaf Soltani Bibi Sedigheh Fazly Bazzaz Farzin Hadizadeh Fatemeh Roodbari Vahid Soheili Source Type: research

< em > In vitro < /em > and < em > in vivo < /em > activities, absorption, tissue distribution and excretion studies of OBP-4, a potential anti- < em > Clostridioides difficile < /em > agent
Antimicrob Agents Chemother. 2021 Apr 5:AAC.00581-21. doi: 10.1128/AAC.00581-21. Online ahead of print.ABSTRACTClostridioides* difficile infection (CDI) is considered to be a major concern of the healthcare system globally with an increasing need for alternative therapies. OBP-4, a new oxazolidinone-fluoroquinolone hybrid with excellent in vitro activities and good safety, shows promising features as an antibacterial agent. Here, we further evaluated the in vitro and in vivo activities of OBP-4 against C. difficile, and its absorption, distribution and excretion (ADE) profiles in rats. In vitro assays indicated OBP-4 was a...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Lili Liu Xuzheng Zhou Bing Li Fusheng Cheng Haifeng Cui Jing Li Jiyu Zhang Source Type: research

Trends of antimicrobial resistance and combination susceptibility testing of cystic fibrosis multidrug-resistant < em > Pseudomonas aeruginosa: < /em > A ten-year update
Antimicrob Agents Chemother. 2021 Apr 5:AAC.02483-20. doi: 10.1128/AAC.02483-20. Online ahead of print.ABSTRACTBackground: Antimicrobial combination therapy is a time/resource- intensive procedure commonly employed in the treatment of cystic fibrosis (CF) pulmonary exacerbations caused by P. aeruginosa Ten years ago the most promising antimicrobial combinations were proposed, but there has since been the introduction of new β-lactam+β-lactamase inhibitor antimicrobial combinations. The aims of this study were i) to compare in vitro activity of these new antimicrobials with other anti-pseudomonals agents and sugge...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Ijeoma N Okoliegbe Karolin Hijazi Kim Cooper Corinne Ironside Ian M Gould Source Type: research

< em > In vitro < /em > Susceptibility of Multidrug-Resistant < em > Pseudomonas aeruginosa < /em > following Treatment-emergent Resistance to Ceftolozane-tazobactam
Antimicrob Agents Chemother. 2021 Apr 5:AAC.00084-21. doi: 10.1128/AAC.00084-21. Online ahead of print.ABSTRACTWe compared the in vitro susceptibility of multidrug-resistant Pseudomonas aeruginosa isolates collected before and after treatment-emergent resistance to ceftolozane-tazobactam. Median baseline and post-exposure ceftolozane-tazobactam MICs were 2 and 64 μg/mL, respectively. Whole-genome sequencing identified treatment-emergent mutations in ampC among 79% (11/14) of paired isolates. AmpC mutations were associated with cross-resistance to ceftazidime-avibactam, but increased susceptibility to piperacillin-tazoba...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Abigail M Rubio Ellen G Kline Chelsea E Jones Liang Chen Barry N Kreiswirth M Hong Nguyen Cornelius J Clancy Vaughn S Cooper Ghady Haidar Daria Van Tyne Ryan K Shields Source Type: research

The role of synonymous mutations in the evolution of TEM β-lactamase genes
Antimicrob Agents Chemother. 2021 Apr 5:AAC.00018-21. doi: 10.1128/AAC.00018-21. Online ahead of print.ABSTRACTNonsynonymous mutations are well documented in TEM β-lactamases. The resulting amino acid changes often alter the conferred phenotype from broad spectrum (2b) conferred by TEM-1 to extended spectrum (2be), inhibitor resistant (2br), or both extended spectrum and inhibitor resistant (2ber). The encoding bla TEM genes also deviate in numerous synonymous mutations, which are not well understood. bla TEM-3 (2be), bla TEM-33 (2br), and bla TEM-109 (2ber) were studied in comparison to bla TEM-1 bla TEM-33 was chose...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Mohammad Faheem Charles J Zhang Monica N Morris Juergen Pleiss Peter Oelschlaeger Source Type: research

Novel Specific Metallo- ß-lactamase Inhibitor, ANT2681, Restores Meropenem Activity to Clinically Effective Levels Against NDM-Positive Enterobacterales
Antimicrob Agents Chemother. 2021 Apr 5:AAC.00203-21. doi: 10.1128/AAC.00203-21. Online ahead of print.ABSTRACTThe global dissemination of metallo-ß-lactamase (MBL)-producing carbapenem resistant Enterobacterales (CRE) is a serious public health concern. Specifically, NDM (New Delhi MBL) has been a major cause of carbapenem therapy failures in recent years, particularly as effective treatments for serine-ß-lactamase (SBL)-producing Enterobacterales are now commercially available. Since the NDM gene is carried on promiscuous plasmids encoding multiple additional resistance determinants, a large proportion of NDM...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Magdalena Zalacain Clarisse Lozano Agustina Llanos Nicolas Sprynski Thomas Valmont Cyntia De Piano David Davies Simon Leiris Carole Sable Adeline Ledoux Ian Morrissey Marc Lemonnier Martin Everett Source Type: research

Identification of a novel ciprofloxacin tolerance gene, < em > aciT, < /em > which contributes to filamentation in < em > Acinetobacter baumannii < /em >
Antimicrob Agents Chemother. 2021 Apr 5:AAC.01400-20. doi: 10.1128/AAC.01400-20. Online ahead of print.ABSTRACTFluoroquinolones are one of the most prescribed broad-spectrum antibiotics. However, their effectiveness is being compromised by high rates of resistance in clinically important organisms including Acinetobacter baumannii We sought to investigate the transcriptomic and proteomic responses of the clinical A. baumannii strain AB5075-UW upon exposure to sub-inhibitory concentrations of ciprofloxacin. Our transcriptomics and proteomics analysis found that the most highly expressed genes and proteins were components of...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Varsha Naidu Bhumika Shah Karthik S Kamath Hsin-Ya Chien Stephanie Nagy Alaska Pokhrel Mark Molloy Karl A Hassan Ian T Paulsen Source Type: research

Dosage individualization of linezolid: precision dosing of linezolid to optimise efficacy and minimise toxicity
Antimicrob Agents Chemother. 2021 Apr 5:AAC.02490-20. doi: 10.1128/AAC.02490-20. Online ahead of print.ABSTRACTHigh interindividual variability in the pharmacokinetics (PK) of linezolid has been described, which results in an unacceptably high proportion of patients with either suboptimal or potentially toxic concentrations following the administration of a fixed regimen. The aim of this study was to develop a population pharmacokinetic model of linezolid and use this to build and validate alogorithms for individualised dosing.A retrospective pharmacokinetic analysis was performed using data from 338 hospitalized patients ...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: S Luque W Hope L Sorli R Mu ñoz-Bermudez N Campillo J Barcel ó F Álvarez-Lerma J P Horcajada J R Masclans-Enviz M Neely S Grau Source Type: research

Azoles susceptibility profiles of more than 9,000 clinical yeast isolates belonging to 40 common and rare species
Antimicrob Agents Chemother. 2021 Apr 5:AAC.02615-20. doi: 10.1128/AAC.02615-20. Online ahead of print.ABSTRACTInvasive yeast infections represent a major global public health issue and only few antifungal agents are available. Azoles are one of the classes of antifungals used for treatment of invasive candidiasis. The determination of antifungal susceptibility profiles using standardized methods is important to identify resistant isolates and to uncover the potential emergence of intrinsically-resistant species. We here report data on 9,319 clinical isolates belonging to 40 pathogenic yeast species recovered in France ove...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Marie Desnos-Ollivier Olivier Lortholary St éphane Bretagne Fran çoise Dromer French Mycoses Study Group Source Type: research

Co-production of Tet(X7) conferring high-level tigecycline resistance, fosfomycin FosA4 and colistin Mcr-1.1 in < em > Escherichia coli < /em > strains from chickens in Egypt
Antimicrob Agents Chemother. 2021 Apr 5:AAC.02084-20. doi: 10.1128/AAC.02084-20. Online ahead of print.ABSTRACTThe plasmid-mediated tet(X7) conferring high-level tigecycline resistance was identified in five mcr-1.1-positive Escherichia coli strains [ST10 (n=3), and ST155 (n=2)] isolated from chickens, Egypt. Two fosfomycin-resistant fosA4-carrying IncFII plasmids (⁓79 kb in size) were detected. Transposase ISCR3 (IS91 family) is syntenic with tet(X7) in all isolates suggesting its role in the mobilization of tet(X7). To our knowledge, this is the first global report of (ST4)-IncHI2 plasmids co-carrying tet(X7) and mcr-1...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Ahmed M Soliman Hazem Ramadan Hoda Zarad Yo Sugawara Liansheng Yu Motoyuki Sugai Toshi Shimamoto Lari M Hiott Jonathan G Frye Charlene R Jackson Tadashi Shimamoto Source Type: research

< em > Physiological responses of < /em > < em > Aspergillus niger < /em > < em > challenged with itraconazole < /em >
Antimicrob Agents Chemother. 2021 Apr 5:AAC.02549-20. doi: 10.1128/AAC.02549-20. Online ahead of print.ABSTRACTAspergillus niger is an opportunistic pathogen commonly found in a variety of indoor and outdoor environments. An environmental isolate of A. niger from a pig farm were resistant to itraconazole and in-depth investigations were conducted to better understand cellular responses during growth when exposed to an antifungal.Using a combination of cultivation techniques, antibiotic stress-testing, and label-free proteomics, this study has investigated the physiological and metabolic responses of A. niger to sublethal l...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Jan Struckmann Poulsen Anne Mette Madsen John Kerr White Jeppe Lund Nielsen Source Type: research

Distinguishing < em > bla < /em > < sub > KPC < /sub > -gene-containing IncF plasmids from epidemiologically related and unrelated Enterobacteriaceae based on short- and long-read sequence data
This study aimed to evaluate the performance of three approaches to distinguish epidemiologically related from unrelated bla KPC-containing pKpQiL-like IncFII(k2)-IncFIB(pQiL) plasmids.METHOD: Epidemiologically related isolates, were short- and long-read whole genome sequenced. A hybrid assembly was performed and plasmid sequences were extracted from the assembly graph. Epidemiologically unrelated plasmid sequences were extracted from the GenBank. Pairwise comparisons were performed of epidemiologically related and unrelated plasmids based on SNP differences using snippy, phylogenetic distance using Roary and using a simil...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Joep J J M Stohr Marjolein F Q Kluytmans-van den Bergh Veronica A T C Weterings John W A Rossen Jan A J W Kluytmans Source Type: research

Vitamin E and K < sub > 1 < /sub > as anti-quorum sensing agents against < em > Pseudomonas aeruginosa < /em > : A new insight
Antimicrob Agents Chemother. 2021 Apr 5:AAC.01342-20. doi: 10.1128/AAC.01342-20. Online ahead of print.ABSTRACTToday, anti-virulence compounds which attenuate bacterial pathogenicity and have no interference with bacterial viability or growth are introduced as next generation of antibacterial agents. However, the development of such compounds that can be used by humans is restricted by various factors, including the need for extensive economic investments, the inability of many molecules to penetrate the membrane of Gram-negative bacteria, or unfavorable pharmacological properties and cytotoxicity.Here, we take a new and d...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Sadaf Soltani Bibi Sedigheh Fazly Bazzaz Farzin Hadizadeh Fatemeh Roodbari Vahid Soheili Source Type: research

< em > In vitro < /em > and < em > in vivo < /em > activities, absorption, tissue distribution and excretion studies of OBP-4, a potential anti- < em > Clostridioides difficile < /em > agent
Antimicrob Agents Chemother. 2021 Apr 5:AAC.00581-21. doi: 10.1128/AAC.00581-21. Online ahead of print.ABSTRACTClostridioides* difficile infection (CDI) is considered to be a major concern of the healthcare system globally with an increasing need for alternative therapies. OBP-4, a new oxazolidinone-fluoroquinolone hybrid with excellent in vitro activities and good safety, shows promising features as an antibacterial agent. Here, we further evaluated the in vitro and in vivo activities of OBP-4 against C. difficile, and its absorption, distribution and excretion (ADE) profiles in rats. In vitro assays indicated OBP-4 was a...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Lili Liu Xuzheng Zhou Bing Li Fusheng Cheng Haifeng Cui Jing Li Jiyu Zhang Source Type: research

Trends of antimicrobial resistance and combination susceptibility testing of cystic fibrosis multidrug-resistant < em > Pseudomonas aeruginosa: < /em > A ten-year update
Antimicrob Agents Chemother. 2021 Apr 5:AAC.02483-20. doi: 10.1128/AAC.02483-20. Online ahead of print.ABSTRACTBackground: Antimicrobial combination therapy is a time/resource- intensive procedure commonly employed in the treatment of cystic fibrosis (CF) pulmonary exacerbations caused by P. aeruginosa Ten years ago the most promising antimicrobial combinations were proposed, but there has since been the introduction of new β-lactam+β-lactamase inhibitor antimicrobial combinations. The aims of this study were i) to compare in vitro activity of these new antimicrobials with other anti-pseudomonals agents and sugge...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Ijeoma N Okoliegbe Karolin Hijazi Kim Cooper Corinne Ironside Ian M Gould Source Type: research

< em > In vitro < /em > Susceptibility of Multidrug-Resistant < em > Pseudomonas aeruginosa < /em > following Treatment-emergent Resistance to Ceftolozane-tazobactam
Antimicrob Agents Chemother. 2021 Apr 5:AAC.00084-21. doi: 10.1128/AAC.00084-21. Online ahead of print.ABSTRACTWe compared the in vitro susceptibility of multidrug-resistant Pseudomonas aeruginosa isolates collected before and after treatment-emergent resistance to ceftolozane-tazobactam. Median baseline and post-exposure ceftolozane-tazobactam MICs were 2 and 64 μg/mL, respectively. Whole-genome sequencing identified treatment-emergent mutations in ampC among 79% (11/14) of paired isolates. AmpC mutations were associated with cross-resistance to ceftazidime-avibactam, but increased susceptibility to piperacillin-tazoba...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Abigail M Rubio Ellen G Kline Chelsea E Jones Liang Chen Barry N Kreiswirth M Hong Nguyen Cornelius J Clancy Vaughn S Cooper Ghady Haidar Daria Van Tyne Ryan K Shields Source Type: research

The role of synonymous mutations in the evolution of TEM β-lactamase genes
Antimicrob Agents Chemother. 2021 Apr 5:AAC.00018-21. doi: 10.1128/AAC.00018-21. Online ahead of print.ABSTRACTNonsynonymous mutations are well documented in TEM β-lactamases. The resulting amino acid changes often alter the conferred phenotype from broad spectrum (2b) conferred by TEM-1 to extended spectrum (2be), inhibitor resistant (2br), or both extended spectrum and inhibitor resistant (2ber). The encoding bla TEM genes also deviate in numerous synonymous mutations, which are not well understood. bla TEM-3 (2be), bla TEM-33 (2br), and bla TEM-109 (2ber) were studied in comparison to bla TEM-1 bla TEM-33 was chose...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Mohammad Faheem Charles J Zhang Monica N Morris Juergen Pleiss Peter Oelschlaeger Source Type: research

Novel Specific Metallo- ß-lactamase Inhibitor, ANT2681, Restores Meropenem Activity to Clinically Effective Levels Against NDM-Positive Enterobacterales
Antimicrob Agents Chemother. 2021 Apr 5:AAC.00203-21. doi: 10.1128/AAC.00203-21. Online ahead of print.ABSTRACTThe global dissemination of metallo-ß-lactamase (MBL)-producing carbapenem resistant Enterobacterales (CRE) is a serious public health concern. Specifically, NDM (New Delhi MBL) has been a major cause of carbapenem therapy failures in recent years, particularly as effective treatments for serine-ß-lactamase (SBL)-producing Enterobacterales are now commercially available. Since the NDM gene is carried on promiscuous plasmids encoding multiple additional resistance determinants, a large proportion of NDM...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Magdalena Zalacain Clarisse Lozano Agustina Llanos Nicolas Sprynski Thomas Valmont Cyntia De Piano David Davies Simon Leiris Carole Sable Adeline Ledoux Ian Morrissey Marc Lemonnier Martin Everett Source Type: research

Identification of a novel ciprofloxacin tolerance gene, < em > aciT, < /em > which contributes to filamentation in < em > Acinetobacter baumannii < /em >
Antimicrob Agents Chemother. 2021 Apr 5:AAC.01400-20. doi: 10.1128/AAC.01400-20. Online ahead of print.ABSTRACTFluoroquinolones are one of the most prescribed broad-spectrum antibiotics. However, their effectiveness is being compromised by high rates of resistance in clinically important organisms including Acinetobacter baumannii We sought to investigate the transcriptomic and proteomic responses of the clinical A. baumannii strain AB5075-UW upon exposure to sub-inhibitory concentrations of ciprofloxacin. Our transcriptomics and proteomics analysis found that the most highly expressed genes and proteins were components of...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Varsha Naidu Bhumika Shah Karthik S Kamath Hsin-Ya Chien Stephanie Nagy Alaska Pokhrel Mark Molloy Karl A Hassan Ian T Paulsen Source Type: research

Dosage individualization of linezolid: precision dosing of linezolid to optimise efficacy and minimise toxicity
Antimicrob Agents Chemother. 2021 Apr 5:AAC.02490-20. doi: 10.1128/AAC.02490-20. Online ahead of print.ABSTRACTHigh interindividual variability in the pharmacokinetics (PK) of linezolid has been described, which results in an unacceptably high proportion of patients with either suboptimal or potentially toxic concentrations following the administration of a fixed regimen. The aim of this study was to develop a population pharmacokinetic model of linezolid and use this to build and validate alogorithms for individualised dosing.A retrospective pharmacokinetic analysis was performed using data from 338 hospitalized patients ...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: S Luque W Hope L Sorli R Mu ñoz-Bermudez N Campillo J Barcel ó F Álvarez-Lerma J P Horcajada J R Masclans-Enviz M Neely S Grau Source Type: research

Azoles susceptibility profiles of more than 9,000 clinical yeast isolates belonging to 40 common and rare species
Antimicrob Agents Chemother. 2021 Apr 5:AAC.02615-20. doi: 10.1128/AAC.02615-20. Online ahead of print.ABSTRACTInvasive yeast infections represent a major global public health issue and only few antifungal agents are available. Azoles are one of the classes of antifungals used for treatment of invasive candidiasis. The determination of antifungal susceptibility profiles using standardized methods is important to identify resistant isolates and to uncover the potential emergence of intrinsically-resistant species. We here report data on 9,319 clinical isolates belonging to 40 pathogenic yeast species recovered in France ove...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Marie Desnos-Ollivier Olivier Lortholary St éphane Bretagne Fran çoise Dromer French Mycoses Study Group Source Type: research

Co-production of Tet(X7) conferring high-level tigecycline resistance, fosfomycin FosA4 and colistin Mcr-1.1 in < em > Escherichia coli < /em > strains from chickens in Egypt
Antimicrob Agents Chemother. 2021 Apr 5:AAC.02084-20. doi: 10.1128/AAC.02084-20. Online ahead of print.ABSTRACTThe plasmid-mediated tet(X7) conferring high-level tigecycline resistance was identified in five mcr-1.1-positive Escherichia coli strains [ST10 (n=3), and ST155 (n=2)] isolated from chickens, Egypt. Two fosfomycin-resistant fosA4-carrying IncFII plasmids (⁓79 kb in size) were detected. Transposase ISCR3 (IS91 family) is syntenic with tet(X7) in all isolates suggesting its role in the mobilization of tet(X7). To our knowledge, this is the first global report of (ST4)-IncHI2 plasmids co-carrying tet(X7) and mcr-1...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Ahmed M Soliman Hazem Ramadan Hoda Zarad Yo Sugawara Liansheng Yu Motoyuki Sugai Toshi Shimamoto Lari M Hiott Jonathan G Frye Charlene R Jackson Tadashi Shimamoto Source Type: research

< em > Physiological responses of < /em > < em > Aspergillus niger < /em > < em > challenged with itraconazole < /em >
Antimicrob Agents Chemother. 2021 Apr 5:AAC.02549-20. doi: 10.1128/AAC.02549-20. Online ahead of print.ABSTRACTAspergillus niger is an opportunistic pathogen commonly found in a variety of indoor and outdoor environments. An environmental isolate of A. niger from a pig farm were resistant to itraconazole and in-depth investigations were conducted to better understand cellular responses during growth when exposed to an antifungal.Using a combination of cultivation techniques, antibiotic stress-testing, and label-free proteomics, this study has investigated the physiological and metabolic responses of A. niger to sublethal l...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Jan Struckmann Poulsen Anne Mette Madsen John Kerr White Jeppe Lund Nielsen Source Type: research

Distinguishing < em > bla < /em > < sub > KPC < /sub > -gene-containing IncF plasmids from epidemiologically related and unrelated Enterobacteriaceae based on short- and long-read sequence data
This study aimed to evaluate the performance of three approaches to distinguish epidemiologically related from unrelated bla KPC-containing pKpQiL-like IncFII(k2)-IncFIB(pQiL) plasmids.METHOD: Epidemiologically related isolates, were short- and long-read whole genome sequenced. A hybrid assembly was performed and plasmid sequences were extracted from the assembly graph. Epidemiologically unrelated plasmid sequences were extracted from the GenBank. Pairwise comparisons were performed of epidemiologically related and unrelated plasmids based on SNP differences using snippy, phylogenetic distance using Roary and using a simil...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Joep J J M Stohr Marjolein F Q Kluytmans-van den Bergh Veronica A T C Weterings John W A Rossen Jan A J W Kluytmans Source Type: research

Vitamin E and K < sub > 1 < /sub > as anti-quorum sensing agents against < em > Pseudomonas aeruginosa < /em > : A new insight
Antimicrob Agents Chemother. 2021 Apr 5:AAC.01342-20. doi: 10.1128/AAC.01342-20. Online ahead of print.ABSTRACTToday, anti-virulence compounds which attenuate bacterial pathogenicity and have no interference with bacterial viability or growth are introduced as next generation of antibacterial agents. However, the development of such compounds that can be used by humans is restricted by various factors, including the need for extensive economic investments, the inability of many molecules to penetrate the membrane of Gram-negative bacteria, or unfavorable pharmacological properties and cytotoxicity.Here, we take a new and d...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Sadaf Soltani Bibi Sedigheh Fazly Bazzaz Farzin Hadizadeh Fatemeh Roodbari Vahid Soheili Source Type: research

< em > In vitro < /em > and < em > in vivo < /em > activities, absorption, tissue distribution and excretion studies of OBP-4, a potential anti- < em > Clostridioides difficile < /em > agent
Antimicrob Agents Chemother. 2021 Apr 5:AAC.00581-21. doi: 10.1128/AAC.00581-21. Online ahead of print.ABSTRACTClostridioides* difficile infection (CDI) is considered to be a major concern of the healthcare system globally with an increasing need for alternative therapies. OBP-4, a new oxazolidinone-fluoroquinolone hybrid with excellent in vitro activities and good safety, shows promising features as an antibacterial agent. Here, we further evaluated the in vitro and in vivo activities of OBP-4 against C. difficile, and its absorption, distribution and excretion (ADE) profiles in rats. In vitro assays indicated OBP-4 was a...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Lili Liu Xuzheng Zhou Bing Li Fusheng Cheng Haifeng Cui Jing Li Jiyu Zhang Source Type: research

Trends of antimicrobial resistance and combination susceptibility testing of cystic fibrosis multidrug-resistant < em > Pseudomonas aeruginosa: < /em > A ten-year update
Antimicrob Agents Chemother. 2021 Apr 5:AAC.02483-20. doi: 10.1128/AAC.02483-20. Online ahead of print.ABSTRACTBackground: Antimicrobial combination therapy is a time/resource- intensive procedure commonly employed in the treatment of cystic fibrosis (CF) pulmonary exacerbations caused by P. aeruginosa Ten years ago the most promising antimicrobial combinations were proposed, but there has since been the introduction of new β-lactam+β-lactamase inhibitor antimicrobial combinations. The aims of this study were i) to compare in vitro activity of these new antimicrobials with other anti-pseudomonals agents and sugge...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Ijeoma N Okoliegbe Karolin Hijazi Kim Cooper Corinne Ironside Ian M Gould Source Type: research

< em > In vitro < /em > Susceptibility of Multidrug-Resistant < em > Pseudomonas aeruginosa < /em > following Treatment-emergent Resistance to Ceftolozane-tazobactam
Antimicrob Agents Chemother. 2021 Apr 5:AAC.00084-21. doi: 10.1128/AAC.00084-21. Online ahead of print.ABSTRACTWe compared the in vitro susceptibility of multidrug-resistant Pseudomonas aeruginosa isolates collected before and after treatment-emergent resistance to ceftolozane-tazobactam. Median baseline and post-exposure ceftolozane-tazobactam MICs were 2 and 64 μg/mL, respectively. Whole-genome sequencing identified treatment-emergent mutations in ampC among 79% (11/14) of paired isolates. AmpC mutations were associated with cross-resistance to ceftazidime-avibactam, but increased susceptibility to piperacillin-tazoba...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Abigail M Rubio Ellen G Kline Chelsea E Jones Liang Chen Barry N Kreiswirth M Hong Nguyen Cornelius J Clancy Vaughn S Cooper Ghady Haidar Daria Van Tyne Ryan K Shields Source Type: research

The role of synonymous mutations in the evolution of TEM β-lactamase genes
Antimicrob Agents Chemother. 2021 Apr 5:AAC.00018-21. doi: 10.1128/AAC.00018-21. Online ahead of print.ABSTRACTNonsynonymous mutations are well documented in TEM β-lactamases. The resulting amino acid changes often alter the conferred phenotype from broad spectrum (2b) conferred by TEM-1 to extended spectrum (2be), inhibitor resistant (2br), or both extended spectrum and inhibitor resistant (2ber). The encoding bla TEM genes also deviate in numerous synonymous mutations, which are not well understood. bla TEM-3 (2be), bla TEM-33 (2br), and bla TEM-109 (2ber) were studied in comparison to bla TEM-1 bla TEM-33 was chose...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Mohammad Faheem Charles J Zhang Monica N Morris Juergen Pleiss Peter Oelschlaeger Source Type: research

Novel Specific Metallo- ß-lactamase Inhibitor, ANT2681, Restores Meropenem Activity to Clinically Effective Levels Against NDM-Positive Enterobacterales
Antimicrob Agents Chemother. 2021 Apr 5:AAC.00203-21. doi: 10.1128/AAC.00203-21. Online ahead of print.ABSTRACTThe global dissemination of metallo-ß-lactamase (MBL)-producing carbapenem resistant Enterobacterales (CRE) is a serious public health concern. Specifically, NDM (New Delhi MBL) has been a major cause of carbapenem therapy failures in recent years, particularly as effective treatments for serine-ß-lactamase (SBL)-producing Enterobacterales are now commercially available. Since the NDM gene is carried on promiscuous plasmids encoding multiple additional resistance determinants, a large proportion of NDM...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Magdalena Zalacain Clarisse Lozano Agustina Llanos Nicolas Sprynski Thomas Valmont Cyntia De Piano David Davies Simon Leiris Carole Sable Adeline Ledoux Ian Morrissey Marc Lemonnier Martin Everett Source Type: research

Identification of a novel ciprofloxacin tolerance gene, < em > aciT, < /em > which contributes to filamentation in < em > Acinetobacter baumannii < /em >
Antimicrob Agents Chemother. 2021 Apr 5:AAC.01400-20. doi: 10.1128/AAC.01400-20. Online ahead of print.ABSTRACTFluoroquinolones are one of the most prescribed broad-spectrum antibiotics. However, their effectiveness is being compromised by high rates of resistance in clinically important organisms including Acinetobacter baumannii We sought to investigate the transcriptomic and proteomic responses of the clinical A. baumannii strain AB5075-UW upon exposure to sub-inhibitory concentrations of ciprofloxacin. Our transcriptomics and proteomics analysis found that the most highly expressed genes and proteins were components of...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Varsha Naidu Bhumika Shah Karthik S Kamath Hsin-Ya Chien Stephanie Nagy Alaska Pokhrel Mark Molloy Karl A Hassan Ian T Paulsen Source Type: research

Dosage individualization of linezolid: precision dosing of linezolid to optimise efficacy and minimise toxicity
Antimicrob Agents Chemother. 2021 Apr 5:AAC.02490-20. doi: 10.1128/AAC.02490-20. Online ahead of print.ABSTRACTHigh interindividual variability in the pharmacokinetics (PK) of linezolid has been described, which results in an unacceptably high proportion of patients with either suboptimal or potentially toxic concentrations following the administration of a fixed regimen. The aim of this study was to develop a population pharmacokinetic model of linezolid and use this to build and validate alogorithms for individualised dosing.A retrospective pharmacokinetic analysis was performed using data from 338 hospitalized patients ...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: S Luque W Hope L Sorli R Mu ñoz-Bermudez N Campillo J Barcel ó F Álvarez-Lerma J P Horcajada J R Masclans-Enviz M Neely S Grau Source Type: research

Azoles susceptibility profiles of more than 9,000 clinical yeast isolates belonging to 40 common and rare species
Antimicrob Agents Chemother. 2021 Apr 5:AAC.02615-20. doi: 10.1128/AAC.02615-20. Online ahead of print.ABSTRACTInvasive yeast infections represent a major global public health issue and only few antifungal agents are available. Azoles are one of the classes of antifungals used for treatment of invasive candidiasis. The determination of antifungal susceptibility profiles using standardized methods is important to identify resistant isolates and to uncover the potential emergence of intrinsically-resistant species. We here report data on 9,319 clinical isolates belonging to 40 pathogenic yeast species recovered in France ove...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Marie Desnos-Ollivier Olivier Lortholary St éphane Bretagne Fran çoise Dromer French Mycoses Study Group Source Type: research

Co-production of Tet(X7) conferring high-level tigecycline resistance, fosfomycin FosA4 and colistin Mcr-1.1 in < em > Escherichia coli < /em > strains from chickens in Egypt
Antimicrob Agents Chemother. 2021 Apr 5:AAC.02084-20. doi: 10.1128/AAC.02084-20. Online ahead of print.ABSTRACTThe plasmid-mediated tet(X7) conferring high-level tigecycline resistance was identified in five mcr-1.1-positive Escherichia coli strains [ST10 (n=3), and ST155 (n=2)] isolated from chickens, Egypt. Two fosfomycin-resistant fosA4-carrying IncFII plasmids (⁓79 kb in size) were detected. Transposase ISCR3 (IS91 family) is syntenic with tet(X7) in all isolates suggesting its role in the mobilization of tet(X7). To our knowledge, this is the first global report of (ST4)-IncHI2 plasmids co-carrying tet(X7) and mcr-1...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Ahmed M Soliman Hazem Ramadan Hoda Zarad Yo Sugawara Liansheng Yu Motoyuki Sugai Toshi Shimamoto Lari M Hiott Jonathan G Frye Charlene R Jackson Tadashi Shimamoto Source Type: research

< em > Physiological responses of < /em > < em > Aspergillus niger < /em > < em > challenged with itraconazole < /em >
Antimicrob Agents Chemother. 2021 Apr 5:AAC.02549-20. doi: 10.1128/AAC.02549-20. Online ahead of print.ABSTRACTAspergillus niger is an opportunistic pathogen commonly found in a variety of indoor and outdoor environments. An environmental isolate of A. niger from a pig farm were resistant to itraconazole and in-depth investigations were conducted to better understand cellular responses during growth when exposed to an antifungal.Using a combination of cultivation techniques, antibiotic stress-testing, and label-free proteomics, this study has investigated the physiological and metabolic responses of A. niger to sublethal l...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Jan Struckmann Poulsen Anne Mette Madsen John Kerr White Jeppe Lund Nielsen Source Type: research

Distinguishing < em > bla < /em > < sub > KPC < /sub > -gene-containing IncF plasmids from epidemiologically related and unrelated Enterobacteriaceae based on short- and long-read sequence data
This study aimed to evaluate the performance of three approaches to distinguish epidemiologically related from unrelated bla KPC-containing pKpQiL-like IncFII(k2)-IncFIB(pQiL) plasmids.METHOD: Epidemiologically related isolates, were short- and long-read whole genome sequenced. A hybrid assembly was performed and plasmid sequences were extracted from the assembly graph. Epidemiologically unrelated plasmid sequences were extracted from the GenBank. Pairwise comparisons were performed of epidemiologically related and unrelated plasmids based on SNP differences using snippy, phylogenetic distance using Roary and using a simil...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Joep J J M Stohr Marjolein F Q Kluytmans-van den Bergh Veronica A T C Weterings John W A Rossen Jan A J W Kluytmans Source Type: research

Vitamin E and K < sub > 1 < /sub > as anti-quorum sensing agents against < em > Pseudomonas aeruginosa < /em > : A new insight
Antimicrob Agents Chemother. 2021 Apr 5:AAC.01342-20. doi: 10.1128/AAC.01342-20. Online ahead of print.ABSTRACTToday, anti-virulence compounds which attenuate bacterial pathogenicity and have no interference with bacterial viability or growth are introduced as next generation of antibacterial agents. However, the development of such compounds that can be used by humans is restricted by various factors, including the need for extensive economic investments, the inability of many molecules to penetrate the membrane of Gram-negative bacteria, or unfavorable pharmacological properties and cytotoxicity.Here, we take a new and d...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Sadaf Soltani Bibi Sedigheh Fazly Bazzaz Farzin Hadizadeh Fatemeh Roodbari Vahid Soheili Source Type: research

< em > In vitro < /em > and < em > in vivo < /em > activities, absorption, tissue distribution and excretion studies of OBP-4, a potential anti- < em > Clostridioides difficile < /em > agent
Antimicrob Agents Chemother. 2021 Apr 5:AAC.00581-21. doi: 10.1128/AAC.00581-21. Online ahead of print.ABSTRACTClostridioides* difficile infection (CDI) is considered to be a major concern of the healthcare system globally with an increasing need for alternative therapies. OBP-4, a new oxazolidinone-fluoroquinolone hybrid with excellent in vitro activities and good safety, shows promising features as an antibacterial agent. Here, we further evaluated the in vitro and in vivo activities of OBP-4 against C. difficile, and its absorption, distribution and excretion (ADE) profiles in rats. In vitro assays indicated OBP-4 was a...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Lili Liu Xuzheng Zhou Bing Li Fusheng Cheng Haifeng Cui Jing Li Jiyu Zhang Source Type: research

Trends of antimicrobial resistance and combination susceptibility testing of cystic fibrosis multidrug-resistant < em > Pseudomonas aeruginosa: < /em > A ten-year update
Antimicrob Agents Chemother. 2021 Apr 5:AAC.02483-20. doi: 10.1128/AAC.02483-20. Online ahead of print.ABSTRACTBackground: Antimicrobial combination therapy is a time/resource- intensive procedure commonly employed in the treatment of cystic fibrosis (CF) pulmonary exacerbations caused by P. aeruginosa Ten years ago the most promising antimicrobial combinations were proposed, but there has since been the introduction of new β-lactam+β-lactamase inhibitor antimicrobial combinations. The aims of this study were i) to compare in vitro activity of these new antimicrobials with other anti-pseudomonals agents and sugge...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Ijeoma N Okoliegbe Karolin Hijazi Kim Cooper Corinne Ironside Ian M Gould Source Type: research

< em > In vitro < /em > Susceptibility of Multidrug-Resistant < em > Pseudomonas aeruginosa < /em > following Treatment-emergent Resistance to Ceftolozane-tazobactam
Antimicrob Agents Chemother. 2021 Apr 5:AAC.00084-21. doi: 10.1128/AAC.00084-21. Online ahead of print.ABSTRACTWe compared the in vitro susceptibility of multidrug-resistant Pseudomonas aeruginosa isolates collected before and after treatment-emergent resistance to ceftolozane-tazobactam. Median baseline and post-exposure ceftolozane-tazobactam MICs were 2 and 64 μg/mL, respectively. Whole-genome sequencing identified treatment-emergent mutations in ampC among 79% (11/14) of paired isolates. AmpC mutations were associated with cross-resistance to ceftazidime-avibactam, but increased susceptibility to piperacillin-tazoba...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Abigail M Rubio Ellen G Kline Chelsea E Jones Liang Chen Barry N Kreiswirth M Hong Nguyen Cornelius J Clancy Vaughn S Cooper Ghady Haidar Daria Van Tyne Ryan K Shields Source Type: research

The role of synonymous mutations in the evolution of TEM β-lactamase genes
Antimicrob Agents Chemother. 2021 Apr 5:AAC.00018-21. doi: 10.1128/AAC.00018-21. Online ahead of print.ABSTRACTNonsynonymous mutations are well documented in TEM β-lactamases. The resulting amino acid changes often alter the conferred phenotype from broad spectrum (2b) conferred by TEM-1 to extended spectrum (2be), inhibitor resistant (2br), or both extended spectrum and inhibitor resistant (2ber). The encoding bla TEM genes also deviate in numerous synonymous mutations, which are not well understood. bla TEM-3 (2be), bla TEM-33 (2br), and bla TEM-109 (2ber) were studied in comparison to bla TEM-1 bla TEM-33 was chose...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Mohammad Faheem Charles J Zhang Monica N Morris Juergen Pleiss Peter Oelschlaeger Source Type: research

Novel Specific Metallo- ß-lactamase Inhibitor, ANT2681, Restores Meropenem Activity to Clinically Effective Levels Against NDM-Positive Enterobacterales
Antimicrob Agents Chemother. 2021 Apr 5:AAC.00203-21. doi: 10.1128/AAC.00203-21. Online ahead of print.ABSTRACTThe global dissemination of metallo-ß-lactamase (MBL)-producing carbapenem resistant Enterobacterales (CRE) is a serious public health concern. Specifically, NDM (New Delhi MBL) has been a major cause of carbapenem therapy failures in recent years, particularly as effective treatments for serine-ß-lactamase (SBL)-producing Enterobacterales are now commercially available. Since the NDM gene is carried on promiscuous plasmids encoding multiple additional resistance determinants, a large proportion of NDM...
Source: Antimicrobial Agents and Chemotherapy - April 6, 2021 Category: Microbiology Authors: Magdalena Zalacain Clarisse Lozano Agustina Llanos Nicolas Sprynski Thomas Valmont Cyntia De Piano David Davies Simon Leiris Carole Sable Adeline Ledoux Ian Morrissey Marc Lemonnier Martin Everett Source Type: research