Article
Microbiology
Vincenzo Di Pilato, Noemi Aiezza, Valentina Viaggi, Alberto Antonelli, Luigi Principe, Tommaso Giani, Francesco Luzzaro, Gian Maria Rossolini
Summary: This study characterized a Klebsiella pneumoniae isolate with high-level resistance to ceftazidime-avibactam due to the presence of KPC-53, a variant of KPC-3 with unique genetic features. Whole-genome sequencing revealed the presence of two copies of blaKPC-53 on different plasmids, shedding light on the mechanisms of resistance to ceftazidime-avibactam.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Microbiology
Lin Wang, Weiyi Shen, Rong Zhang, Jiachang Cai
Summary: This study identified a novel ceftazidime-avibactam-resistant KPC-2 variant, KPC-123, in a Citrobacter koseri isolated from a patient in a Chinese hospital. The KPC-123 variant showed high-level resistance to ceftazidime and ceftazidime/avibactam, but remained susceptible to carbapenems. Whole-genome sequencing and genomic analysis revealed the transfer and in vivo evolution of the bla(KPC)-carrying plasmid. Active surveillance is needed to prevent and control the dissemination of ceftazidime/avibactam resistance.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Microbiology
Jacqueline Findlay, Laurent Poirel, Mario Juhas, Patrice Nordmann
Summary: This study evaluated the impact of KPC variants on CZA resistance, finding increased susceptibility to cephalosporins and carbapenems but increased resistance to ceftazidime and piperacillin-tazobactam. The KPC variants exhibited increased affinity towards ceftazidime and slightly decreased sensitivity to avibactam, impacting CZA resistance while concurrently negatively impacting carbapenemase activities.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Infectious Diseases
Ke Ma, Yu Feng, Zhiyong Zong
Summary: Aztreonam/avibactam has additional coverage for metallo-beta-lactamases compared with ceftazidime/avibactam, but some strains may develop resistance to aztreonam/avibactam while remaining susceptible to ceftazidime/avibactam.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2022)
Article
Microbiology
Yanqin Huang, Karol Sokolowski, Amisha Rana, Nidhi Singh, Jiping Wang, Ke Chen, Yinzhi Lang, Jieqiang Zhou, Neera Kadiyala, Fiorella Krapp, Egon A. Ozer, Alan R. Hauser, Jian Li, Jurgen B. Bulitta, Zackery P. Bulman
Summary: Combining aminoglycosides with ceftazidime/avibactam shows promising synergy against KPC-producing Klebsiella pneumoniae infections, leading to reduced bacterial counts. Selecting aminoglycosides based on genes or susceptibilities can enhance the pharmacodynamic activity of the combination therapy.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Microbiology
Alessandra Carattoli, Gabriele Arcari, Giulia Bibbolino, Federica Sacco, Dario Tomolillo, Federica Maria Di Lella, Maria Trancassini, Luigi Faino, Mario Venditti, Guido Antonelli, Giammarco Raponi
Summary: A study conducted in a university hospital in Rome, Italy identified multiple CZA-resistant KPC-3 protein variants, including novel variants that had not been reported before. These variants showed different sensitivities and activities to antibiotics, possibly due to mutations caused by amino acid substitutions, insertions, and deletions.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Microbiology
Agnes B. Jousset, Saoussen Oueslati, Cecile Emeraud, Remy A. Bonnin, Laurent Dortet, Bogdan I. Iorga, Thierry Naas
Summary: Resistance to the combination of ceftazidime (CAZ) and avibactam (AVI) is increasing, with a CAZ-AVI-resistant Klebsiella pneumoniae strain reported here. This strain, belonging to the high-risk sequence type 307 (ST307) clone, produces Klebsiella pneumoniae carbapenemase 39 (KPC-39), a single-amino-acid variant of KPC3. The study found that KPC-39 has lost carbapenemase activity but shows increased affinity for CAZ, suggesting potential silent dissemination in European healthcare settings.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Microbiology
Yuexing Tu, Dairong Wang, Yiwei Zhu, Jiayan Li, Yan Jiang, Wenhao Wu, Xi Li, Hua Zhou
Summary: For the first time, we reported a KPC variant, KPC-90, in a clinical ST463 CRPA strain with CZA resistance. CZA resistance was mediated by a 2 amino acid insertion outside the KPC omega-loop region in CRPA. Our study further emphasized that CZA resistance caused by bla(KPC) gene mutation could be selected in CRPA after CZA therapy. Considering the widespread presence of the ST463 CRPA strain in China, clinicians should pay attention to the risk of the development of CZA resistance in CRPA strains under treatment pressure.
MICROBIOLOGY SPECTRUM
(2022)
Article
Infectious Diseases
Charalampos Zarras, Elias Iosifidis, Maria Simitsopoulou, Styliani Pappa, Angeliki Kontou, Emmanuel Roilides, Anna Papa
Summary: This article reports a case of neonatal sepsis caused by CAZ/AVI-resistant bla(KPC-2)-harboring Klebsiella pneumoniae carrying bla(VEB-25), and describes the use of a customized active surveillance program and enhanced infection control measures. The emergence of bla(VEB-25) signals horizontal plasmid transfer in hospital facilities and highlights the importance of monitoring for novel resistance mechanisms. Molecular diagnostics can guide appropriate antimicrobial therapy and the early implementation of infection control measures against antimicrobial resistance.
Article
Microbiology
Xiangning Huang, Siquan Shen, Fan Chang, Xin Liu, Jinxi Yue, Ning Xie, Lin Yin, Fupin Hu, Daiwen Xiao
Summary: The emergence of new KPC variants leading to treatment failure with ceftazidime-avibactam presents a new challenge for clinical anti-infection treatment. In this study, a ceftazidime-avibactam-resistant K. pneumoniae strain carrying a novel KPC-134 variant was reported. The study highlights the importance of timely identification of KPC variants and effective anti-infective therapy for saving infected patients.
MICROBIOLOGY SPECTRUM
(2023)
Article
Microbiology
Diego Faccone, Juan M. de Mendieta, Ezequiel Albornoz, Magali Chavez, Fabiana Genero, Mariano Echegorry, Paola Ceriana, Andrea Mora, Christine Seah, Alejandra Corso, Roberto G. Melano, Fernando Pasteran
Summary: A ceftazidime-avibactam-resistant KPC-producing Pseudomonas aeruginosa strain, belonging to the high-risk clone ST235/O11, was identified in Argentina. Whole-genome sequencing revealed a D179Y substitution in the Omega loop of KPC-3, corresponding to KPC-31 integrated at the chromosome. Most commonly used carbapenemase detection assays failed to identify the isolate as a KPC producer.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Infectious Diseases
Meng Yu, Qingzheng Wei, Weiqing Song, Jiangshui Yuan
Summary: This study aimed to investigate the development of resistance to ceftazidime-avibactam and carbapenems in a K. pneumonia strain expressing a novel KPC-2 variant. The results showed that the KPC-49 mutant strain was resistant to both ceftazidime-avibactam and carbapenems. Experimental whole genome sequencing combined with bioinformatics analysis was used to understand the drug resistance mechanisms of the mutant strains.
INFECTION AND DRUG RESISTANCE
(2023)
Article
Microbiology
Francois Lebreton, Brendan W. Corey, Christi L. McElheny, Alina Iovleva, Lan Preston, Katie R. Margulieux, Robert J. Cybulski, Patrick Mc Gann, Yohei Doi, Jason W. Bennett
Summary: KPC-82 is a KPC-2 variant found in a carbapenem-nonsusceptible Citrobacter koseri, conferring high-level resistance to ceftazidime-avibactam. The bla(KPC-82) gene is carried on a chromosomally integrated Tn4401 transposon, resulting in a two-amino-acid insertion caused by a nucleotide tandem repeat. Despite decreased carbapenemase activity in a heterologous background, KPC-82 remains susceptible to carbapenem/beta-lactamase inhibitor combinations.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Infectious Diseases
Krisztina M. Papp-Wallace, Melissa D. Barnes, Magdalena A. Taracila, Christopher R. Bethel, Joseph D. Rutter, Elise T. Zeiser, Katherine Young, Robert A. Bonomo
Summary: Ceftazidime-avibactam is ineffective against KPC-2 D179 variants, but imipenem-relebactam can overcome their resistance. The D179Y variant is unable to hydrolyze imipenem, while the D179N variant has a slower rate. Acyl complexes are less prevalent with the D179Y variant compared to the D179N variant. Imipenem-relebactam shows promise for treating clinical isolates harboring D179 variants of KPC-2.
Article
Infectious Diseases
Karoline Knudsen List, Mette Kolpen, Kasper Norskov Kragh, Godefroid Charbon, Stine Radmer, Frank Hansen, Anders Lobner-Olesen, Niels Frimodt-Moller, Frederik Boetius Hertz
Summary: The study evaluated the efficacy of mecillinam in combination with either avibactam or ceftazidime/avibactam against carbapenemase-producing clinical isolates. The combination substantially reduced MICs and showed significant log-CFU reductions in time-kill and in vivo experiments, indicating a notable effect on most types of CPEs, both in vitro and in vivo.
Article
Microbiology
Laura Dabos, Joanna E. Raczynska, Pierre Bogaerts, Agustin Zavala, Delphine Girlich, Remy A. Bonnin, Laurent Dortet, Aurelie Peyrat, Pascal Retailleau, Bogdan I. Iorga, Mariusz Jaskolski, Youri Glupczynski, Thierry Naas
Summary: OXA-48-producing Enterobacterales have disseminated globally, with several variants reported, differing by a few amino acid substitutions or deletions, mostly in the /35-/36 loop region. OXA-517, a natural variant of OXA-48, with an Arg214Lys substitution and a deletion in the β5-β6 loop, has the ability to hydrolyze extended-spectrum cephalosporins and carbapenems. This study highlights the remarkable ability of OXA-48-like carbapenemases to evolve through mutation/deletion in the β5-β6 loop to expand their hydrolysis spectrum.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Letter
Infectious Diseases
Sandrine Bernabeu, Remy A. Bonnin, Laurent Dortet
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Article
Infectious Diseases
Agnes B. Jousset, Sandrine Bernabeu, Cecile Emeraud, Remy A. Bonnin, Alexandra Lomont, Jean Ralph Zahar, Audrey Merens, Christophe Isnard, Nathalie Soismier, Eric Farfour, Vincent Fihman, Nicolas Yin, Olivier Barraud, Herve Jacquier, Anne-Gaelle Ranc, Frederic Laurent, Stephane Corvec, Louise Ruffier d'Epenoux, Emmanuelle Bille, Nicolas Degand, Chloe Plouzeau, Thomas Guillard, Vincent Cattoir, Asaf Mizrahi, Antoine Grillon, Frederic Janvier, Cecile Le Brun, Marlene Amara, Mathilda Bastide, Alban Lemonnier, Laurent Dortet
Summary: This study aimed to provide susceptibility data on a large series of Enterobacterales since the revision of EUCAST categorization break-points in 2020. The results showed that Ceftolozane-tazobactam (C/T) had a susceptibility rate of 88% in Enterobacterales infections, with higher susceptibility in 3GC-resistant strains and lower susceptibility in CRE strains. This prospective study highlights the importance of C/T in the treatment of infections.
JOURNAL OF GLOBAL ANTIMICROBIAL RESISTANCE
(2023)
Article
Infectious Diseases
Remy A. Bonnin, Sandrine Bernabeu, Cecile Emeraud, Thierry Naas, Delphine Girlich, Agnes B. Jousset, Laurent Dortet
Summary: This study demonstrated the high in vitro efficacy of ceftazidime/avibactam, imipenem/relebactam, and to a lesser extent meropenem/vaborbactam against carbapenem-resistant non-carbapenemase-producing Enterobacterales. Testing all beta-lactam/beta-lactamase inhibitor combinations is crucial for carbapenem-resistant Enterobacterales (CRE) as resistance to one combination does not predict resistance to another, depending on the resistance mechanisms involved.
Article
Medicine, General & Internal
Alessandra Natale, Saoussen Oueslati, Alice Rochard, Sien Ombelet, Daniel Lopez-Baez, Liselotte Hardy, Jane Cunningham, Celine Franquesa, Olivier Vandenberg, Jean-Baptiste Ronat, Thierry Naas
Summary: Culture media is essential for detecting and isolating bacterial pathogens in clinical bacteriology, but preparing media in low-resource settings can be challenging. InTray cassettes are convenient, ready-to-use media preparations that can serve as an alternative. This study evaluated the use of two InTray media for subculture alternative in diagnosing bloodstream infections. The InTray Muller-Hinton chocolate had a high sensitivity and specificity, and the InTray Colorex Screen was effective in detecting mixed flora.
Article
Biochemistry & Molecular Biology
Emile Dupuy, Sander Egbert Van der Verren, Jiusheng Lin, Mark Alan Wilson, Alix Vincent Daschsbeck, Felipe Viela, Emmanuell Latour, Alexandr Gennaris, Didier Vertommen, Yves Frederic Dufrene, Bogdan Iuliu Lorga, Camille Veronique Goemans, Han Remaut, Jean-Francois Collet
Summary: Hsp60 chaperonins and their Hsp10 cofactors facilitate protein folding. This study reveals that the bacterial chaperonin GroEL forms a stable complex with the chaperedoxin CnoX, and CnoX likely functions as a redox quality-control plugin for GroEL. The findings suggest that Hsp60 molecular plugins have been conserved through evolution, as proteins sharing structural features with CnoX exist in eukaryotes.
Letter
Infectious Diseases
Agnes B. Jousset, Corentin Poignon, Seher Yilmaz, Alexandre Bleibtreu, Cecile Emeraud, Delphine Girlich, Thierry Naas, Jerome Robert, Remy A. Bonnin, Laurent Dortet
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Article
Infectious Diseases
Rita Elias, Anton Spadar, Antoni P. A. Hendrickx, Remy A. Bonnin, Laurent Dortet, Margarida Pinto, Jody E. Phelan, Isabel Portugal, Susana Campino, Gabriela Jorge da Silva, Taane G. Clark, Aida Duarte, Joao Perdigao
Summary: This study characterized the genomic diversity and international dissemination of CRKP strains from tertiary care hospitals in Lisbon, Portugal. Two genomic clusters, ST13/GC1 and ST17/GC2, were identified. Additionally, an emerging OXA-181/ST17-producing strain in Portugal and the ongoing international dissemination of a KPC-3/ST13-producing clone were highlighted.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Editorial Material
Microbiology
Thierry Naas, Laura Dabos, Remy A. Bonnin
Review
Chemistry, Medicinal
Elsa Denakpo, Thierry Naas, Bogdan I. Iorga
EXPERT OPINION ON THERAPEUTIC PATENTS
(2023)
Article
Infectious Diseases
Lydia Galvez-Benitez, Jose Manuel Ortiz de la Rosa, Angel Rodriguez-Villodres, Carlos S. Casimiro-Soriguer, Irene Molina-Panadero, Rocio Alvarez-Marin, Remy A. Bonnin, Thierry Naas, Jeronimo Pachon, Jose Miguel Cisneros, Jose Antonio Lepe, Younes Smani
Summary: This study aimed to identify the mechanisms underlying Piperacillin-tazobactam resistance (P/T-R) in Escherichia coli. The results showed that P/T-R isolates had a higher copy number of the bla(TEM) gene, generated by three different genetic events. In addition, reduced expression of OmpC was observed in two P/T-R strains. This study provides important insights into the acquisition of P/T-R in E. coli, which is crucial for effective treatment and prevention of resistant microorganisms.
JOURNAL OF INFECTION
(2023)
Article
Infectious Diseases
Mariam Rima, Niels Pfennigwerth, Martina Cremanns, Katarina Cirnski, Saoussen Oueslati, Soeren G. Gatermann, Nicola d'Amelio, Jennifer Herrmann, Rolf Mueller, Thierry Naas
Summary: The development of novel antibiotics is crucial to combat the growing problem of antibiotic resistance. In this study, the activity spectrum of cystobactamids and chelocardins, two promising classes of molecules with different modes of action, was determined. These molecules showed potent activities against clinically relevant Gram-negative and Gram-positive bacteria, including multi-drug resistant strains. The findings suggest that cystobactamid CN-DM-861 and chelocardin CDCHD have interesting antibiotic activities on MDR or XDR bacteria without cross-resistance to clinically relevant antibiotics.
Article
Public, Environmental & Occupational Health
Dina Daaboul, Issmat I. Kassem, Khaled El Omari, Monzer Hamze, Fouad Daboussi, Saoussen Oueslati, Thierry Naas, Marwan Osman
Summary: Antimicrobial resistance disproportionately affects displaced and vulnerable populations, highlighting the need for proactive One Health strategies.
JOURNAL OF TRAVEL MEDICINE
(2023)