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JOURNAL ARTICLE
Taegum Lee, Seongyeon Lee, Mi Kyoung Kim, Joong Hoon Ahn, Ji Sun Park, Hwi Won Seo, Ki-Ho Park, Youhoon Chong
The discovery of safe and efficient inhibitors against efflux pumps as well as metallo-β-lactamases (MBL) is one of the main challenges in the development of multidrug-resistant (MDR) reversal agents which can be utilized in the treatment of carbapenem-resistant Gram-negative bacteria. In this study, we have identified that introduction of an ethylene-linked sterically demanding group at the 3-OH position of the previously reported MDR reversal agent di-F-Q endows the resulting compounds with hereto unknown multitarget inhibitory activity against both efflux pumps and broad-spectrum β-lactamases including difficult-to-inhibit MBLs...
April 23, 2024: ACS Infectious Diseases
#2
JOURNAL ARTICLE
Natalia Słabisz, Patrycja Leśnik, Jarosław Janc, Miłosz Fidut, Marzenna Bartoszewicz, Ruth Dudek-Wicher, Urszula Nawrot
BACKGROUND: Due to the growing resistance to routinely used antibiotics, the search for new antibiotics or their combinations with effective inhibitors against multidrug-resistant microorganisms is ongoing. In our study, we assessed the in vitro drug susceptibility of Klebsiella pneumoniae strains producing New Delhi metallo-β-lactamases (NDM) to antibiotics included in the Infectious Diseases Society of America (IDSA) and European Society of Clinical Microbiology and Infectious Diseases (ESCMID) recommendations...
2024: Frontiers in Microbiology
#3
JOURNAL ARTICLE
Yu-Lin Lee, Chun-Eng Liu, Hung-Jen Tang, Yu-Tsung Huang, Yao-Shen Chen, Po-Ren Hsueh
BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has contributed to the spread of antimicrobial resistance, including carbapenem-resistant Enterobacterales. METHODS: This study utilized data from the Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance program in Taiwan. Enterobacterales from patients with bloodstream infections (BSIs) were collected and subjected to antimicrobial susceptibility testing and β-lactamase gene detection using a multiplex PCR assay...
April 7, 2024: Journal of Microbiology Immunology and Infection
#4
JOURNAL ARTICLE
Yi-Tan Li, Xian-di Chen, Ying-Yi Guo, Shan-Wen Lin, Ming-Zhen Wang, Jian-Bo Xu, Xiao-Hu Wang, Guo-Hua He, Xi-Xi Tan, Chao Zhuo, Zhi-Wei Lin
Carbapenem-resistant Acinetobacter baumannii (CRAB) is resistant to almost all antibiotics. Eravacycline, a newer treatment option, has the potential to treat CRAB infections, however, the mechanism by which CRAB isolates develop resistance to eravacycline has yet to be clarified. This study sought to investigate the features and mechanisms of eravacycline heteroresistance among CRAB clinical isolates. A total of 287 isolates were collected in China from 2020 to 2022. The minimum inhibitory concentration (MIC) of eravacycline and other clinically available agents against A...
2024: Frontiers in Cellular and Infection Microbiology
#5
JOURNAL ARTICLE
Ilyas Alav, Parisa Pordelkhaki, Pedro Ernesto de Resende, Hannah Partington, Simon Gibbons, Rianne M Lord, Michelle M C Buckner
Antimicrobial resistance genes (ARG), such as extended-spectrum β-lactamase (ESBL) and carbapenemase genes, are commonly carried on plasmids. Plasmids can transmit between bacteria, disseminate globally, and cause clinically important resistance. Therefore, targeting plasmids could reduce ARG prevalence, and restore the efficacy of existing antibiotics. Cobalt complexes possess diverse biological activities, including antimicrobial and anticancer properties. However, their effect on plasmid conjugation has not been explored yet...
April 6, 2024: Scientific Reports
#6
JOURNAL ARTICLE
Douglas L Huseby, Sha Cao, Edouard Zamaratski, Sanjeewani Sooriyaarachchi, Shabbir Ahmad, Terese Bergfors, Laura Krasnova, Juris Pelss, Martins Ikaunieks, Einars Loza, Martins Katkevics, Olga Bobileva, Helena Cirule, Baiba Gukalova, Solveiga Grinberga, Maria Backlund, Ivailo Simoff, Anna T Leber, Talía Berruga-Fernández, Dmitry Antonov, Vivekananda R Konda, Stefan Lindström, Gustav Olanders, Peter Brandt, Pawel Baranczewski, Carina Vingsbo Lundberg, Edgars Liepinsh, Edgars Suna, T Alwyn Jones, Sherry L Mowbray, Diarmaid Hughes, Anders Karlén
Here, we describe the identification of an antibiotic class acting via LpxH, a clinically unexploited target in lipopolysaccharide synthesis. The lipopolysaccharide synthesis pathway is essential in most Gram-negative bacteria and there is no analogous pathway in humans. Based on a series of phenotypic screens, we identified a hit targeting this pathway that had activity on efflux-defective strains of Escherichia coli . We recognized common structural elements between this hit and a previously published inhibitor, also with activity against efflux-deficient bacteria...
April 9, 2024: Proceedings of the National Academy of Sciences of the United States of America
#7
JOURNAL ARTICLE
Troy Skwor, Dan Christopher Jones, Caitlin Cahak, Ryan J Newton
Antibiotic resistance remains one of the most pressing public health issues facing the world today. At the forefront of this battle lies the ever-increasing identification of extended-spectrum beta-lactamases and carbapenemases within human pathogens, conferring resistance towards broad-spectrum and last-resort antimicrobials. This study was prompted due to the identification of a pathogenic Aeromonas hydrophila isolate (strain MAH-4) collected from abdominal fluid, which presented a robust resistance pattern against second-, third-, and fourth-generation cephalosporins, ertapenem, ciprofloxacin, gentamicin, levofloxacin and moxifloxacin, and beta lactam/beta-lactamase inhibitor combinations...
February 29, 2024: Microorganisms
#8
REVIEW
Stefanos Ferous, Cleo Anastassopoulou, Vassiliki Pitiriga, Georgia Vrioni, Athanasios Tsakris
Carbapenem-resistant Gram-negative bacterial infections are a major public health threat due to the limited therapeutic options available. The introduction of the new β-lactam/β-lactamase inhibitors (BL/BLIs) has, however, altered the treatment options for such pathogens. Thus, four new BL/BLI combinations-namely, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam, and ceftolozane/tazobactam-have been approved for infections attributed to carbapenem-resistant Enterobacterales species and Pseudomonas aeruginosa ...
March 21, 2024: Antibiotics
#9
JOURNAL ARTICLE
Yinping Wang, Huangdu Hu, Qiucheng Shi, Ping Zhang, Dongdong Zhao, Yan Jiang, Yunsong Yu
Abstract Carbapenem-resistant Enterobacterales (CRE), specifically those resistant to only ertapenem among carbapenems (ETP-mono-resistant), are increasingly reported, while the optimal therapy options remain uncertain. To investigate the prevalence and characteristics of ETP-mono-resistant CRE, CRE strains were systematically collected from 102 hospitals across China between 2018 and 2021. A 1:1 randomized matching study was conducted with ETP-mono-resistant strains to meropenem- and/or imipenem-resistant (MEM/IPM-resistant) strains...
March 22, 2024: Emerging Microbes & Infections
#10
JOURNAL ARTICLE
Christina K Lin, Alex Page, Sarah Lohsen, Ali A Haider, Jesse Waggoner, Gillian Smith, Ahmed Babiker, Jesse T Jacob, Jessica Howard-Anderson, Sarah W Satola
BACKGROUND: Heteroresistance (HR), the presence of antibiotic-resistant subpopulations within a primary isogenic population, may be a potentially overlooked contributor to newer β-lactam/β-lactamase inhibitor (BL/BLI) treatment failure in carbapenem-resistant Enterobacterales (CRE) infections. OBJECTIVES: To determine rates of susceptibility and HR to BL/BLIs ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam in clinical CRE isolates...
April 2024: JAC-antimicrobial resistance
#11
JOURNAL ARTICLE
Tania Blanco-Martín, Isaac Alonso-García, Lucía González-Pinto, Michelle Outeda-García, Paula Guijarro-Sánchez, Inmaculada López-Hernández, María Pérez-Vázquez, Belén Aracil, Lorena López-Cerero, Pablo Fraile-Ribot, Antonio Oliver, Juan Carlos Vázquez-Ucha, Alejandro Beceiro, Germán Bou, Jorge Arca-Suárez
OBJECTIVES: To analyze the impact of the most clinically relevant β-lactamases and their interplay with low outer membrane permeability on the activity of cefiderocol, ceftazidime/avibactam, aztreonam/avibactam, cefepime/enmetazobactam, cefepime/taniborbactam, cefepime/zidebactam, imipenem/relebactam, meropenem/vaborbactam, meropenem/xeruborbactam and meropenem/nacubactam against recombinant E. coli strains. METHODS: We constructed 82 Escherichia coli laboratory transformants expressing the main β-lactamases circulating in Enterobacterales (70 expressing single β-lactamase and 12 producing double carbapenemase) under high (E...
March 19, 2024: International Journal of Antimicrobial Agents
#12
JOURNAL ARTICLE
Nichole K Stewart, Marta Toth, Pojun Quan, Michael Beer, John D Buynak, Clyde A Smith, Sergei B Vakulenko
Carbapenem antibiotics are used as a last-resort treatment for infections caused by multidrug-resistant bacteria. The wide spread of carbapenemases in Gram-negative bacteria has severely compromised the utility of these drugs and represents a serious public health threat. To combat carbapenemase-mediated resistance, new antimicrobials and inhibitors of these enzymes are urgently needed. Here, we describe the interaction of the atypically C5α-methyl-substituted carbapenem, NA-1-157, with the GES-5 carbapenemase...
March 21, 2024: ACS Infectious Diseases
#13
JOURNAL ARTICLE
Xinhui Li, Jisheng Zhang, Jianmin Wang, Wenzhang Long, Xushan Liang, Yang Yang, Xue Gong, Jie Li, Longjin Liu, Xiaoli Zhang
Isolates coproducing serine/metallo-carbapenems are a serious emerging public health threat, given their rapid dissemination and the limited number of treatment options. The purposes of this study were to evaluate the in vitro antibacterial activity of novel β-lactam-β-lactamase inhibitor combinations (BLBLIs) against carbapenem-resistant Klebsiella pneumoniae (CRKP) coproducing metallo-β-lactamase and serine-β-lactamase, and to explore their effects in combination with aztreonam, meropenem, or polymyxin in order to identify the best therapeutic options...
2024: Frontiers in Microbiology
#14
JOURNAL ARTICLE
Matías Gálvez-Silva, Patricio Arros, Camilo Berríos-Pastén, Aura Villamil, Paula I Rodas, Ingrid Araya, Rodrigo Iglesias, Pamela Araya, Juan C Hormazábal, Constanza Bohle, Yahua Chen, Yunn-Hwen Gan, Francisco P Chávez, Rosalba Lagos, Andrés E Marcoleta
BACKGROUND: The convergence of hypervirulence and carbapenem resistance in the bacterial pathogen Klebsiella pneumoniae represents a critical global health concern. Hypervirulent K. pneumoniae (hvKp) strains, frequently from sequence type 23 (ST23) and having a K1 capsule, have been associated with severe community-acquired invasive infections. Although hvKp were initially restricted to Southeast Asia and primarily antibiotic-sensitive, carbapenem-resistant hvKp infections are reported worldwide...
March 12, 2024: Biological Research
#15
JOURNAL ARTICLE
Yu Wang, Sylvia A Sapula, Jonathan J Whittall, Jack M Blaikie, Olga Lomovskaya, Henrietta Venter
The increasing rate of carbapenem-resistant bacteria within healthcare environments is an issue of great concern that needs urgent attention. This resistance is driven by metallo-β-lactamases (MBLs), which can catalyse the hydrolysis of almost all clinically available β-lactams and are resistant to all the clinically utilized β-lactamase inhibitors. In this study, an uncharacterized MBL is identified in a multidrug resistant isolate of the opportunistic pathogen, Chryseobacterium indologenes...
March 7, 2024: Communications Biology
#16
JOURNAL ARTICLE
Mahmoud Saad Abdel-Halim, Amira M El-Ganiny, Basem Mansour, Galal Yahya, Hemat K Abd El Latif, Momen Askoura
BACKGROUND: Carbapenems represent the first line treatment of serious infections caused by drug-resistant Klebsiella pneumoniae. Carbapenem-resistant K. pneumoniae (CRKP) is one of the urgent threats to human health worldwide. The current study aims to evaluate the carbapenemase inhibitory potential of coumarin and to test its ability to restore meropenem activity against CRKP. Disk diffusion method was used to test the antimicrobial susceptibility of K. pneumoniae clinical isolates to various antibiotics...
February 27, 2024: BMC Microbiology
#17
JOURNAL ARTICLE
Matteo Boattini, Gabriele Bianco, Laura Iglesias Llorente, Laura Alonso Acero, Daniel Nunes, Miguel Seruca, Vasco Santos Mendes, André Almeida, Paulo Bastos, Ángel Rodríguez-Villodres, Adelina Gimeno Gascón, Ana Verónica Halperin, Rafael Cantón, Maria Nieves Larrosa Escartín, Juan José González-López, Pauline Floch, Clémence Massip, Delphine Chainier, Olivier Barraud, Laurent Dortet, Gaëlle Cuzon, Clément Zancanaro, Assaf Mizrahi, Rogier Schade, Asger Nellemann Rasmussen, Kristian Schønning, Axel Hamprecht, Lukas Schaffarczyk, Stefan Glöckner, Jürgen Rödel, Katalin Kristóf, Ágnes Balonyi, Stefano Mancini, Chantal Quiblier, Teresa Fasciana, Anna Giammanco, Bianca Paglietti, Salvatore Rubino, Ana Budimir, Branka Bedenić, Zana Rubic, Jelena Marinović, Konstantina Gartzonika, Eirini Christaki, Viktoria Eirini Mavromanolaki, Sofia Maraki, Tuğba Yanık Yalçın, Özlem Kurt Azap, Monica Licker, Corina Musuroi, Daniela Talapan, Vrancianu Corneliu Ovidiu, Sara Comini, Patrycja Zalas-Więcek, Anna Michalska, Rossana Cavallo, José Melo Cristino, Cristina Costa
INTRODUCTION: The ESCPM group (Enterobacter species including Klebsiella aerogenes - formerly Enterobacter aerogenes, Serratia species, Citrobacter freundii complex, Providencia species and Morganella morganii) has not yet been incorporated into systematic surveillance programs. METHODS: We conducted a multicentre retrospective observational study analysing all ESCPM strains isolated from blood cultures in 27 European hospitals over a three-year period (2020-2022)...
February 15, 2024: International Journal of Antimicrobial Agents
#18
JOURNAL ARTICLE
Helio S Sader, Cecilia G Carvalhaes, John H Kimbrough, Rodrigo E Mendes, Mariana Castanheira
Aztreonam-avibactam is under clinical development for treatment of infections caused by carbapenem-resistant Enterobacterales (CRE), especially those resistant to recently approved β-lactamase inhibitor combinations (BLICs). We evaluated a large collection of CRE isolates, including those nonsusceptible to ceftazidime-avibactam, meropenem-vaborbactam, and/or imipenem-relebactam. Overall, 24,580 Enterobacterales isolates were consecutively collected (1/patient) in 2020-2022 from 64 medical centres located in Western Europe (W-EU), Eastern Europe (E-EU), Latin America (LATAM), and the Asia-Pacific region (APAC)...
February 12, 2024: International Journal of Antimicrobial Agents
#19
JOURNAL ARTICLE
Nicolas Helsens, Mustafa Sadek, Christophe Le Terrier, Laurent Poirel, Patrice Nordmann
PURPOSE: Carbapenemase-producing Enterobacterales are a growing threat, and very few therapeutic options remain active against those multidrug resistant bacteria. Aztreonam is the molecule of choice against metallo-beta-lactamases (MBL) producers since it is not hydrolyzed by those enzymes, but the co-production of acquired plasmidic cephalosporinases or extended-spectrum β-lactamases leading to aztreonam resistance may reduce the efficacy of this molecule. Hence, the development of the aztreonam-avibactam (AZA) combination provides an interesting therapeutic alternative since avibactam inhibits the activity of both cephalosporinases and extended-spectrum β-lactamases...
February 6, 2024: European Journal of Clinical Microbiology & Infectious Diseases
#20
JOURNAL ARTICLE
Andrew J Fratoni, Matthew L Gethers, David P Nicolau, Joseph L Kuti
Gram-negative antibiotic resistance continues to grow as a global problem due to the evolution and spread of β-lactamases. The early β-lactamase inhibitors (BLIs) are characterized by spectra limited to class A β-lactamases and ineffective against carbapenemases and most extended spectrum β-lactamases. In order to address this therapeutic need, newer BLIs were developed with the goal of treating carbapenemase producing, carbapenem resistant organisms (CRO), specifically targeting the Klebsiella pneumoniae carbapenemase (KPC)...
February 2, 2024: Clinical Infectious Diseases
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