Review
Microbiology
Bela Kocsis, Daniel Gulyas, Dora Szabo
Summary: This review summarizes the characteristics and mechanisms of drug resistance of high-risk Pseudomonas aeruginosa clones from confirmed outbreaks and whole-genome sequence data. Common features such as beta-lactamases production and distribution of metallo-beta-lactamases in different STs are highlighted. The resistance to colistin among P. aeruginosa clones is less developed compared to other mechanisms, while transferable quinolone resistance determinants are frequently reported, with aac(6 ')-Ib-cr variant being the most commonly found.
Article
Infectious Diseases
David C. Bean, David W. Wareham
Summary: This study reported a multidrug-resistant P. aeruginosa strain PA3 from the UK, producing SIM carbapenemase. The strain was resistant to most drugs but susceptible to colistin. The genome sequence revealed the presence of bla(SIM-1).
JOURNAL OF GLOBAL ANTIMICROBIAL RESISTANCE
(2022)
Article
Infectious Diseases
Yue Li, Yiwei Zhu, Wanqing Zhou, Zhongju Chen, Robert A. Moran, Huanhuan Ke, Yu Feng, Willem van Schaik, Han Shen, Jingshu Ji, Zhi Ruan, Xiaoting Hua, Yunsong Yu
Summary: This study characterized AFM-2 and AFM-3 metallo-beta-lactamase from clinical Pseudomonas aeruginosa isolates. The results showed that these enzymes exhibited beta-lactamase activity comparable to NDM-1, and the co-carriage of bla(AFM) and bla(KPC) genes rendered P. aeruginosa resistant to antipseudomonal beta-lactams. Furthermore, the association of bla(AFM) genes with translocatable genetic elements and plasmids highlighted their potential for dissemination.
CLINICAL MICROBIOLOGY AND INFECTION
(2022)
Article
Microbiology
Alba Ruedas-Lopez, Isaac Alonso-Garcia, Cristina Lasarte-Monterrubio, Paula Guijarro-Sanchez, Eva Gato, Juan Carlos Vazquez-Ucha, Juan Andres Vallejo, Pablo Arturo Fraile-Ribot, Begona Fernandez-Perez, David Velasco, Jose Maria Gutierrez-Urbon, Marina Oviano, Alejandro Beceiro, Concepcion Gonzalez-Bello, Antonio Oliver, Jorge Arca-Suarez, German Bou
Summary: This study aimed to analyze the resistance mechanisms of ceftolozane-tazobactam and ceftazidime-avibactam in multidrug-resistant or extensively drug-resistant P. aeruginosa isolates. The findings revealed that most of the resistant isolates were recovered after treatment with ceftolozane-tazobactam or ceftazidime-avibactam. Chromosomal mutations and specific gene substitutions were identified as the main resistance mechanisms. The study emphasized the potential selection of MDR/XDR P. aeruginosa strains producing certain variants or metallo-beta-lactamases by cephalosporin/beta-lactamase inhibitors, and encouraged judicious use of these agents.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Infectious Diseases
Anka Lucic, Tika R. Malla, Karina Calvopina, Catherine L. Tooke, Jurgen Brem, Michael A. McDonough, James Spencer, Christopher J. Schofield
Summary: This study investigated the reaction of the carbapenem biapenem with different subclasses of beta-lactamases. The results showed the formation of enamine and various types of imine products. The findings support the idea that prolonging the lifetime of beta-lactamase carbapenem complexes by optimizing the tautomerization process could lead to improved carbapenems.
Article
Pharmacology & Pharmacy
Yan Guo, Hongtao Liu, Mengge Yang, Rui Ding, Yawen Gao, Xiaodi Niu, Xuming Deng, Jianfeng Wang, Haihua Feng, Jiazhang Qiu
Summary: The study identified dexrazoxane, embelin, candesartan cilexetil, and nordihydroguaiaretic acid as promising carbapenem adjuvants against metallo-β-lactamase-producing carbapenem-resistant bacterial pathogens. These drugs inhibit the activity of metallo-β-lactamases and show in vitro synergistic bactericidal effect with meropenem.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Microbiology
Michaela Simon, Roman G. Gerlach, Yvonne Pfeifer, Niels Pfennigwerth, Soren G. Gatermann, Agnes Schroeder, Andreas Hiergeist, Axel Hamprecht, Tamara Ruegamer, Andre Gessner, Jonathan Jantsch
Summary: The study evaluated the effectiveness of a semi-automated antimicrobial susceptibility testing system in detecting ceftazidime-avibactam resistance in carbapenem-resistant, metallo-beta-lactamase-producing bacteria. The system showed good performance in detecting susceptibility to ceftazidime-avibactam, providing a reliable method for identifying phenotypic resistance in these bacteria.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Infectious Diseases
Tomasz Bogiel, Malgorzata Prazynska, Joanna Kwiecinska-Pirog, Agnieszka Mikucka, Eugenia Gospodarek-Komkowska
Summary: The study compared the frequency of selected enzymatic virulence factor genes among non-duplicated carbapenem-resistant P. aeruginosa isolates, finding a higher prevalence of alkaline protease gene and a 37.4% detection rate for neuraminidase-1 gene. Significant differences in the prevalence of lasB and nan1 were observed between MBL-positive and MBL-negative strains.
Article
Chemistry, Medicinal
Yu-Hang Yan, Wenfang Li, Wei Chen, Chao Li, Kai-Rong Zhu, Ji Deng, Qing-Qing Dai, Ling-Ling Yang, Zhenling Wang, Guo-Bo Li
Summary: In this study, the researchers optimized 1H-imidazole-2-carboxylic acid (ICA) derivatives guided by X-ray structure to develop inhibitor 55 that can interact ingeniously with metallo-beta-lactamases (MBLs) and reverse carbapenem resistance. In experiments, inhibitor 55 demonstrated potent antibacterial activity and showed good pharmacokinetics and safety in vivo.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Yongqiang Yang, Yu-Hang Yan, Christopher J. Schofield, Alan McNally, Zhiyong Zong, Guo-Bo Li
Summary: Resistance to beta-lactam antibiotics is a growing concern due to the spread of serine-beta-lactamases (SBLs) and metallo-beta-lactamases (MBLs), which efficiently break down beta-lactam antibiotics. While inhibitors for SBLs have been successful in clinical use, there are currently no inhibitors for MBLs. MBLs are particularly worrisome as they can break down most beta-lactam antibiotics and are rapidly disseminating across bacterial species worldwide.
TRENDS IN MICROBIOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Ying Ge, Peng-Wei Kang, Jia-Qi Li, Han Gao, Le Zhai, Le-Yun Sun, Cheng Chen, Ke-Wu Yang
Summary: The study demonstrated that thiosemicarbazones are valuable scaffolds for developing inhibitors of NDM-1 and drug-resistant bacteria carrying NDM-1, and they also exhibit synergistic antimicrobial effects with other antibiotics, showing strong activity against bacteria harboring NDM-1.
JOURNAL OF ANTIBIOTICS
(2021)
Article
Immunology
Fred C. Tenover, David P. Nicolau, Christian M. Gill
Summary: The article discusses the clinical importance of carbapenem-resistant Pseudomonas aeruginosa (CR-PA) worldwide, including the resistance situation of the pathogen, transmission routes, different types of carbapenemases in various regions, and strategies for optimizing treatment.
EMERGING MICROBES & INFECTIONS
(2022)
Article
Infectious Diseases
Mihret Tilahun, Alemu Gedefie, Habitye Bisetegn, Habtu Debash
Summary: The high prevalence of extended-spectrum beta-lactamase and carbapenemase producing Acinetobacter species and Pseudomonas aeruginosa among hospitalized patients in Dessie Comprehensive Specialized Hospital, Ethiopia is a major concern. Antimicrobial resistance testing revealed a high rate of multidrug resistance among the isolated bacteria.
INFECTION AND DRUG RESISTANCE
(2022)
Article
Infectious Diseases
Gianluca Morroni, Lucia Brescini, Alberto Antonelli, Vincenzo Di Pilato, Sefora Castelletti, Andrea Brenciani, Gloria D'Achille, Marina Mingoia, Eleonora Giovanetti, Simona Fioriti, Annamaria Masucci, Tommaso Giani, Andrea Giacometti, Gian Maria Rossolini, Oscar Cirioni
Summary: A surveillance study conducted in a regional hospital in Italy revealed the presence of Ceftolozane/tazobactam-resistant P. aeruginosa isolates carrying multiple resistance mechanisms acquired by various high-risk clones.
JOURNAL OF GLOBAL ANTIMICROBIAL RESISTANCE
(2022)
Article
Chemistry, Medicinal
Liqiang Hu, Huixin Yang, Tao Yu, Fangfang Chen, Runqiu Liu, Shuyuan Xue, Shuangzhan Zhang, Wuyu Mao, Changge Ji, Hao Wang, Hexin Xie
Summary: This study demonstrates the effectiveness of stereochemically altered cephalosporins as potent inhibitors against NDM-1, a major cause of antibiotic resistance. The findings provide a new approach to combat antibiotic resistance.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
